Journal articles: 'LGALS3'

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Chaney, Heather L., Lindsay F. Grose, Jeanna M. LaBarbara, Adam W. Sirk, Alyssa M. Blancke, Jose M. Sánchez, Claudia Passaro, Patrick Lonergan, and Daniel J. Mathew. "Galectin-1 induces gene and protein expression related to maternal-conceptus immune tolerance in bovine endometrium." Biology of Reproduction 106, no. 3 (November 18, 2021): 487–502. http://dx.doi.org/10.1093/biolre/ioab215.

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Abstract Conceptus secretory factors include galectins, a family of carbohydrate binding proteins that elicit cell adhesion and immune suppression by interacting with intracellular and extracellular glycans. In rodents, galectin-1 (LGALS1) promotes maternal-fetal immune tolerance in the decidua through expansion of tolerogenic cluster of differentiation 11c (CD11c) positive dendritic cells, increased anti-inflammatory interleukin (IL)-10, and activation of forkhead box P3 (FOXP3) positive regulatory T cells (Treg). This study characterized galectin expression in early ruminant conceptuses and endometrium. We also tested the effect of recombinant bovine LGALS1 (rbLGALS1) and progesterone (P4) on endometrial expression of genes and protein related to maternal-conceptus immune tolerance in cattle. Elongating bovine and ovine conceptuses expressed several galectins, particularly, LGALS1, LGALS3, and LGALS8. Within bovine endometrium, expression of LGALS3, LGALS7, and LGALS9 was greater on Day 16 of pregnancy compared to the estrous cycle. Within ovine endometrium, LGALS7 was greater during pregnancy compared to the estrous cycle and endometrium of pregnant sheep tended to have greater LGALS9 and LGALS15. Expression of endometrial LGALS4 was less during pregnancy in sheep. Treating bovine endometrium with rbLGALS1 increased endometrial expression of CD11c, IL-10, and FOXP3, within 24 h. Specifically, within caruncular endometrium, both rbLGALS1 and P4 increased FOXP3, suggesting that both ligands may promote Treg expansion. Using IHC, FOXP3+ cells with a leukocyte phenotype were localized to the bovine uterine stratum compactum near the uterine surface and increased in response to rbLGALS1. We hypothesize that galectins have important functions during establishment of pregnancy in ruminants and bovine conceptus LGALS1 and luteal P4 confer mechanisms of maternal-conceptus immune tolerance in cattle.

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Asiamah, Emmanuel K., Mulumebet Worku, Juan Loor, Mario Vailati Riboni, Zheng Zhou, and Kingsley Ekwemalor. "PSVI-5 Rumen-protected methionine supplementation during the peripartal period reduces the expression of LGALS-1, -3 and -4 in polymorphonuclear leukocytes (PMNL) and secretion of Gal-2 and Gal-12 in plasma of Holstein cows." Journal of Animal Science 97, Supplement_3 (December 2019): 200–201. http://dx.doi.org/10.1093/jas/skz258.413.

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Abstract The objective of this study was to evaluate the effect of methionine(Met) supplementation on genes encoding Galectins (LGALS) and secretion in plasma during the periparturient period. Dairy cows are susceptible to increased incidence and severity of disease during the periparturient period. Impaired polymorphonuclear leukocyte (PMNL) functions such as phagocytosis and pathogen killing capacity contribute to immune dysfunction and disease. Galectins (GALS) are an evolutionarily conserved family of animal lectins important in disease and homeostasis. They behave like pathogen-associated molecular patterns and cell-surface receptors whose activation often results in signaling cascades to activate cells such as PMNL. Fourteen Holstein cows supplemented with either rumen-protected Met (n = 7) or no Met (CON; n = 7) were used. Diets were fed from −21 ± 2 before expected calving date and continued until 30 days postpartum. To evaluate LGALS expression and secretion of Gal, PMNL were isolated from blood and plasma was harvested at -10, +7, and +30 d relative to expected calving. The expression of LGALS1 (P = 0.09), LGALS3 (P = 0.02), and LGALS4 (P = 0.02) was lower in response to Met, but there was no effect on LGALS8, LGALS9, and LGALS12. Met supplementation reduced Gal-2 and Gal-12 secretion in plasma at -10, +7, and +30 d (P < 0.0005 and P < 0.0001 respectively). Methionine supplementation modulates the expression of GAL involved in inflammation and lipolysis in cow blood. Modulation of GAL in PMNL and plasma in response to Met may have implications for the use of dietary interventions to target gene expression in PMNL for improved function and needs further study.

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Xu, Wang-Dong, Qian Wu, Yan-Wei He, An-Fang Huang, You-Yu Lan, Lu Fu, Jie Zhou, and Xiao-Yan Liu. "Gene polymorphisms of LGALS2, LGALS3 and LGALS9 in patients with rheumatoid arthritis." Cellular Immunology 368 (October 2021): 104419. http://dx.doi.org/10.1016/j.cellimm.2021.104419.

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Okumu, L. A., T. Fair, J. Szekeres-Bartho, A. M. O'Doherty, M. A. Crowe, J. F. Roche, P. Lonergan, and N. Forde. "Endometrial expression of progesterone-induced blocking factor and galectins-1, -3, -9, and -3 binding protein in the luteal phase and early pregnancy in cattle." Physiological Genomics 43, no. 14 (July 2011): 903–10. http://dx.doi.org/10.1152/physiolgenomics.00251.2010.

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Progesterone-induced blocking factor (PIBF) and galectins modulate the maternal immune response during pregnancy. We hypothesized that the relative transcript abundance of the above genes would be different during the luteal phase/early pregnancy and would be affected by progesterone supplementation. To further test this, hypothesis protein expression analyses were carried out to evaluate the abundance and localization of LGALS9 and PIBF. Following estrus synchronization, heifers were inseminated ( n = 140) or not ( n = 70). Half the heifers in each status (cyclic or potentially pregnant) were randomly assigned to receive a progesterone-releasing intravaginal device (PRID) on day 3 after estrus, which elevated progesterone concentrations from day 3.5 to 8 ( P < 0.05), resulting in four treatment groups: cyclic and pregnant heifers, each with normal and high progesterone. After confirmation of pregnancy status in inseminated animals, uterine tissue was collected on days 5, 7, 13, or 16 of the luteal phase of the cycle/pregnancy. Gene and protein expression was determined using Q-RT-PCR and IHC, respectively, on 5 heifers per treatment per time point (i.e., 80 in total). Progesterone concentrations did not affect expression of any of the genes ( P > 0.05). LGALS9 and LGALS3BP were expressed at low levels in both cyclic and pregnant endometria until day 13. On day 16, expression increased only in the pregnant heifers ( P < 0.0001). LGALS1 and LGALS3 decreased on day 7 ( P < 0.0001) and remained low until day 16. Pregnancy had no effect on the expression of LGALS1, LGALS3, and PIBF. Additionally, LGALS9 and PIBF proteins were expressed in distinct uterine cell types. These results indicate that the galectins may be involved in uterine receptivity and/or implantation in heifers.

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Sakurai, Takuya, Toshiyuki Fukutomi, Sachiko Yamamoto, Eriko Nozaki, and Takako Kizaki. "Physical Activity Attenuates the Obesity-Induced Dysregulated Expression of Brown Adipokines in Murine Interscapular Brown Adipose Tissue." International Journal of Molecular Sciences 22, no. 19 (September 27, 2021): 10391. http://dx.doi.org/10.3390/ijms221910391.

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In recent years, brown adipose tissue (BAT), which has a high heat-producing capacity, has been confirmed to exist even in adults, and it has become a focal point for the prevention and the improvement of obesity and lifestyle-related diseases. However, the influences of obesity and physical activity (PA) on the fluid factors secreted from BAT (brown adipokines) are not well understood. In this study, therefore, we focused on brown adipokines and investigated the effects of obesity and PA. The abnormal expressions of gene fluid factors such as galectin-3 (Lgals3) and Lgals3 binding protein (Lgals3bp), whose proteins are secreted from HB2 brown adipocytes, were observed in the interscapular BAT of obese mice fed a high-fat diet for 4 months. PA attenuated the abnormalities in the expressions of these genes. Furthermore, although the gene expressions of factors related to brown adipocyte differentiation such as peroxisome proliferator-activated receptor gamma coactivator 1-α were also down-regulated in the BAT of the obese mice, PA suppressed the down-regulation of these factors. On the other hand, lipogenesis was increased more in HB2 cells overexpressing Lgals3 compared with that in control cells, and the overexpression of Lgals3bp decreased the mitochondrial mass. These results indicate that PA attenuates the obesity-induced dysregulated expression of brown adipokines and suggests that Lgals3 and Lgals3bp are involved in brown adipocyte differentiation.

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Ruvolo, Peter, Yihua Qiu, Vivian Ruvolo, Rui-Yu Wang, Zhihong Zeng, Jared Burks, Rongqing Pan, et al. "Role of Mesenchymal Stem Cell Galectin 3 in the AML Tumor Microenvironment." Blood 126, no. 23 (December 3, 2015): 1198. http://dx.doi.org/10.1182/blood.v126.23.1198.1198.

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Abstract Background: Mesenchymal stem cells (MSC) protect acute myeloid leukemia (AML) cells from chemotherapy. Galectin 3 (LGALS3) is a beta-galactoside binding protein that regulates cell adhesion, apoptosis, cell cycle, and mRNA processing. When secreted, LGALS3 can modulate receptor kinase activity, influence cell adhesion, and can suppress immune cells. MSC are a rich source of LGALS3. In the present study we address the role of MSC derived LGALS3 in the leukemia microenvironment. Methods: The expression of LGALS3 and 150 other proteins was examined by reverse phase protein array analysis (RPPA) in AML (N = 106) and healthy donor (N = 71) MSC. To examine the putative role of MSC-derived proteins in therapy resistance, RPPA was used to determine levels of the 151 proteins in MSC obtained at diagnosis and from relapsed/refractory patients relapse. In vitro studies were performed to examine the effects of hypoxia or co-culture with AML cell lines on LGALS3 expression by immunofluorescence (IF) microscopy and immunoblot analysis. MSC containing lentiviral control shRNA or LGALS3 shRNA were used to assess effects of LGALS3 on cell viability, apoptosis, and cell adhesion by flow cytometry assays and effects on survival signaling by immunoblot analysis. Results: LGALS3 levels were found to be higher in AML MSC compared to normal MSC (p = 0.0001). The increase in protein expression was not correlated with gene expression as mRNA levels were similar in AML and normal MSC, suggesting a post-translational mechanism. To identify MSC proteins associated with relapse or refractory status, RPPA was utilized to compare protein expression in MSC from newly diagnosed with those from relapsed and refractory (salvage) patients. RPPA identified LGALS3 as one of only three proteins increased in MSC from relapse/refractory patients. Pearson Correlation of LGALS3 with the other 150 proteins in AML MSC revealed that LGALS3 was negatively correlated with expression of integrin beta 3 and LYN. These 2 proteins were also among the 6 proteins found to have lower expression in salvage as compared to MSC from newly diagnosed patients. LGALS3 positively correlated with 13 proteins including phosphorylated beta-catenin which was also higher in salvage as compared to newly diagnosed AML MSC. . The LGALS3 promoter contains HIF1 alpha response elements. MSC from healthy donors grown in 1% oxygen displayed > 4 fold increase in LGALS3 protein after 24 hours. Hypoxic MSC exhibited a re-localization of LGALS3 from the nucleus to the cytoplasm. LGALS3 activates RAS signaling so hypoxia induced expression and nuclear export of the galectin would be expected to activate diverse survival signaling pathways and would also allow the molecule to be secreted where it could then suppress immune cells. Using in vitro co-culture experiments of MSC with human OCI-AML3 cells to mimic the leukemia microenvironment, LGALS3 levels were induced in MSC suggesting that cross talk from leukemia cells could contribute to the increased LGALS3 levels in MSC cells. The consequences of suppressing LGALS3 in normal MSC were tested using lentivral shRNA. Suppression of LGALS3 resulted in a 2-fold reduction of MYC and S473 phosphorylated AKT, and a 2-fold increase in PPP2R2A (an AKT phosphatase) compared to control shRNA. LGALS3 suppression rendered MSC less adherent to OCI-AML3 cells (~ 50% reduction in MSC with LGALS3 shRNA compared to control shRNA). Conclusions: The data presented here demonstrate that LGALS3 is elevated in AML MSC especially in relapse/refractory samples. Possible mechanisms of up-regulation of LGALS3 in AML MSC may be due to the hypoxic nature of the leukemia microenvironment and/or contact with AML cell. Hypoxia induced nuclear export of the galectin to the cytoplasm could contribute to MSC survival and anti-tumor functions (e.g. suppression of immune cells by secreted galectin). Knock down of LGALS3 in MSC suppresses AKT activation and MYC expression suggesting it has a key role in MSC cell survival. Experiments are underway to determine if MSC derived LGALS3 might impact AML cell homing (as a regulator of cell adhesion) and/or immune surveillance (as a suppressor of T and NK cells). The identification of LGALS3 as an important component of AML MSC suggests that this molecule could be a target in a tumor microenvironment based therapy concept of AML. Disclosures No relevant conflicts of interest to declare.

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Mansorunov, Danzan, Natalya Apanovich, Fatimat Kipkeeva, Maxim Nikulin, Olga Malikhova, Ivan Stilidi, and Alexander Karpukhin. "The Correlation of Ten Immune Checkpoint Gene Expressions and Their Association with Gastric Cancer Development." International Journal of Molecular Sciences 23, no. 22 (November 10, 2022): 13846. http://dx.doi.org/10.3390/ijms232213846.

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In the immunotherapy based on immune checkpoint inhibition (IC), additional ICs are being studied to increase its effectiveness. An almost unstudied feature is the possible co-expression of ICs, which can determine the therapeutic efficacy of their inhibition. For the selection of promising ICs, information on the association of their expression with cancer development may be essential. We have obtained data on the expression correlation of ADAM17, PVR, TDO2, CD274, CD276, CEACAM1, IDO1, LGALS3, LGALS9, and HHLA2 genes in gastric cancer (GC). All but one, TDO2, have other IC genes with co-expression at some stage. At the metastatic stage, the expression of the IDO1 does not correlate with any other gene. The correlations are positive, but the expressions of the CD276 and CEACAM1 genes are negatively correlated. The expression of TDO2 and LGALS3 is associated with GC metastasis. The expression of TDO2 four-fold higher in metastatic tumors than in non-metastatic tumors, but LGALS3 was two-fold lower. The differentiation is associated with IDO1. The revealed features of TDO2, with a significant increase in expression at the metastatic stage and the absence of other IC genes with correlated expression indicates that the prospect of inhibiting TDO2 in metastatic GC. IDO1 may be considered for inhibition in low-differentiated tumors.

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Martins, Luciane, Suzana Garcia Leoni, Celso U. M. Friguglietti, Laura Sterian Ward, Marco Aurélio V. Kulcsar, and Edna Teruko Kimura. "O Polimorfismo no códon 98 do gene de galectina-3 não está associado a tumores benignos e malignos de tiróide." Arquivos Brasileiros de Endocrinologia & Metabologia 50, no. 6 (December 2006): 1075–81. http://dx.doi.org/10.1590/s0004-27302006000600014.

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Galectina-3 é uma proteína multifuncional altamente expressa em câncer de tiróide. O gene de galectina-3 (LGALS3) apresenta vários candidatos a SNPs anotados, no entanto a relação entre estes SNPs e variações fenotípicas específicas relevantes à saúde não foi avaliada. Neste estudo, investigamos SNPs do LGALS3 e uma possível associação destes com a tumorigênese tiroidiana. A presença de SNPs do LGALS3 em linhagens de carcinoma de tiróide (WRO, NPA, TPC-1, ARO), tecidos tiroidianos de 55 pacientes com diagnóstico de bócio multinodular ou carcinoma papilífero e linfócitos do sangue periférico de 45 indivíduos saudáveis foi avaliada por seqüenciamento e SSCP. A análise da seqüência codificadora do LGALS3 mostrou que o sítio T98P apresenta uma grande variação genotípica, visto que observamos os padrões homozigoto (AA ou CC) e heterozigoto (AC). Em linhagens de carcinoma de tiróide, o genótipo da NPA no sítio T98P do LGALS3 é CC, enquanto TPC-1, WRO e ARO são AC. As freqüências genotípicas do T98P do LGALS3 observadas em bócio multinodular (AC= 67%, AA= 23%, CC= 10%) e carcinoma papilífero (AC= 68%, AA= 20%, CC= 12%) foram semelhante à freqüência observada na população controle (AC= 60%, AA= 24%, CC= 16%). Em conclusão, não observamos associação entre o genótipo T98P do LGALS3 e o fenótipo de tumor benigno ou maligno de tiróide.

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Sun, Liqun, Meihua Sun, Ke Ma, and Jiangtao Liu. "Let-7d-5p suppresses inflammatory response in neonatal rats with necrotizing enterocolitis via LGALS3-mediated TLR4/NF-κB signaling pathway." American Journal of Physiology-Cell Physiology 319, no. 6 (December 1, 2020): C967—C979. http://dx.doi.org/10.1152/ajpcell.00571.2019.

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Necrotizing enterocolitis (NEC) is an acute intestinal condition accounting for severe mortality and morbidity in preterm infants. This study aimed to identify the possible roles of let-7d-5p in neonatal rats with NEC. The differentially expressed genes (DEGs) related to NEC were initially screened in silico. After establishment of NEC rat models, measurement of the expression of let-7d-5p, galectin-3 (LGALS3), Toll-like receptor 4 (TLR4), and nuclear factor-κB (NF-κB) as well as proinflammatory cytokines (TNF-α, IL-1β, and IL-6) was conducted. The interaction between let-7d-5p and LGALS3 or argonaute-2 (AGO2) was identified. Gain- and loss-of-function approaches were then performed in an attempt to investigate the regulatory roles of let-7d-5p and LGALS3 in inflammation and cell apoptosis in NEC neonatal rats. Let-7d-5p was poorly expressed, whereas LGALS3, TLR4, and NF-κB were highly expressed, in the intestinal tissues of NEC rats. Overexpression of let-7d-5p resulted in decreased levels of proinflammatory factors in the intestinal tissues of NEC rats. Through sequential experimentation, let-7d-5p was identified to target LGALS3 and bind to AGO2. In addition, LGALS3 silencing or LPS treatment blocked the TLR4/NF-κB signaling pathway, thereby suppressing intestinal epithelial cell apoptosis and inflammation in NEC. Collectively, let-7d-5p might exercise its inhibitory properties in the inflammatory response and intestinal epithelial cell apoptosis in NEC neonatal rats via inactivation of the LGALS3-dependent TLR4/NF-κB signaling pathway.

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Cheng, Chieh-Lung, Hsin-An Hou, Ming-Cheng Lee, Chieh-Yu Liu, Jie-Yang Jhuang, Yan-Jun Lai, Chung-Wu Lin, et al. "Higher bone marrow LGALS3 expression is an independent unfavorable prognostic factor for overall survival in patients with acute myeloid leukemia." Blood 121, no. 16 (April 18, 2013): 3172–80. http://dx.doi.org/10.1182/blood-2012-07-443762.

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Key Points Bone marrow LGALS3 expression is associated with distinct clinical and biological features in patients with acute myeloid leukemia. Higher bone marrow LGALS3 expression is an independent poor prognostic factor for overall survival and may serve as a potential therapeutic target.

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Davis, Richard E., Vivian R. Ruvolo, Zhiqiang Wang, Wencai Ma, Wendy D. Schober, James Rolke, George Tidmarsh, Michael Andreeff, and Peter P. Ruvolo. "GCS-100 Induces Apoptosis of Acute Myeloid Leukemia Cells By Disrupting Galectin-Mediated Survival Signaling." Blood 124, no. 21 (December 6, 2014): 904. http://dx.doi.org/10.1182/blood.v124.21.904.904.

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Abstract Galectins are a family of b-galactoside binding proteins with effects on cell adhesion, apoptosis, cell cycle, and mRNA processing. Galectin-3 (LGALS3) is unique among galectins by having an N terminal region of roughly 130 amino acids that allows for multimerization and binding to other proteins independent of carbohydrate binding. In addition to promoting BCL2 gene expression and mitochondrial integrity, LGALS3 (along with LGALS1) positively regulates RAS signaling and thus stabilizes survival proteins dependent on ERK phosphorylation such as MCL-1. The pro-survival functions of LGALS3 and other galectins suggest that their targeting could be therapeutic for cancers including AML. Indeed, LGALS3 expression is a predictor of poor prognosis in acute myeloid leukemia (AML), as reported by Cheng and colleagues (Blood 2013) for patients with non-M3 AML and CN-AML. The modified pectin GCS-100 (La Jolla Pharmaceutical, San Diego, CA), now in a Phase II clinical trial for chronic kidney disease, binds and blocks the function of LGALS3. We report that GCS-100 suppresses the growth of AML cell lines OCI-AML3, THP-1, and HL60 in vitro as a single agent, at doses under the 250 ug/mL (i.e., within clinically-achievable concentrations). Short-term treatment of cells (i.e., < 6 hr) potently suppressed phosphorylation of AKT and ERK and reduced expression of BCL2 and MCL-1. Because LGALS3 positively regulates anti-apoptotic BCL2 family members, the Raz group has suggested targeting galectins to enhance efficacy of BH3 mimetic drugs (Harazano et al Cancer Metastasis Review 2013). We found that GCS-100 potently synergized with ABT-737 to kill OCI-AML3 cells: while 1 uM ABT-737 or 125 ug/mL GCS-100 reduced total viable cells by ~ 30% and induced apoptosis in < 20% of cells after 48 hr as single agents, their combination at those doses and time point reduced viable cells by ~ 94% and induced apoptosis in ~ 70% of cells. Suppression of LGALS3 by lentiviral shRNA reduced BCL2 gene expression as determined by qRT-PCR and augmented killing with ABT-737. Lentiviral suppression of LGALS3 protected cells from GCS-100 at doses of 250 ug/mL but reduction of the galectin failed to protect cells from higher doses of the drug (i.e., 500 ug/mL). This result suggests other galectins are likely inhibited at higher doses of the agent. We used gene expression profiling (GEP) on Illumina HT12v4 human whole-genome arrays to assess more broadly the molecular effects of inhibiting galectins in AML cell lines OCI-AML3 and THP-1 treated with 250 ug/mL or 500 ug/ml GCS-100 for 24 hr. Data were analyzed by Gene Set Enrichment Analysis (GSEA) using gene sets from the Molecular Signatures Database (www.broadinstitute.org/gsea/msigdb/). GSEA suggested that GCS-100 promotes differentiation and inhibits genes associated with proliferation. Multiple upregulated gene sets suggest that there may be a release of a differentiation block as a result of GCS-100 treatment. Furthermore, two gene sets suggest that GCS-100 behaves similar to a GSK3 inhibitor: Known pathways regulated by GSK3 in hematopoietic stem cells are mTOR and Wnt/beta Catenin. Inhibition of Wnt/beta Catenin can release a differentiation block. Consistent with GCS-100 promoting cell differentiation, lentiviral shRNA reduced LGALS3 protein > 90% in THP-1 cells and increased CD11b expression, suggesting increased differentiation, compared to cells with control shRNA. GCS-100 was tested in an in vitro model of the bone marrow microenvironment using BM-derived mesenchymal stromal cell (MSC). MSC can protect leukemia cells from a variety of clinically relevant chemotherapy drugs including AraC. GCS-100 was effective at killing AML cells despite the presence of MSC. Both THP-1 and OCI-AML3 cells exhibited > 80% and > 60% reduction of viable cells, respectively, despite the presence of MSC when treated with 250 ug/mL GCS-100 for 72 hours. In addition, GCS-100 was found to block adhesion of OCI-AML3 cells to MSC suggesting that GCS-100 could be effective in mobilizing AML cells. In summary, our findings suggest that GCS-100 can induce apoptosis in AML cells as a single agent or in combination with the BH3 mimetic ABT-737. The agent is effective even in the presence of MSC suggesting it could be efficacious in the leukemia niche. These findings suggest GCS-100 could be effective for AML therapy. Disclosures Rolke: La Jolla Pharmaceutical Company: Employment. Tidmarsh:La Jolla Pharmaceutical Company: Employment.

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Fu, Hao, Shaoping Nie, Ping Luo, Yang Ruan, Zichuan Zhang, Huangtai Miao, Xin Li, Songnan Wen, and Rong Bai. "Galectin-3 and acute heart failure: genetic polymorphisms, plasma level, myocardial fibrosis and 1-year outcomes." Biomarkers in Medicine 14, no. 11 (July 2020): 943–54. http://dx.doi.org/10.2217/bmm-2020-0269.

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Aim: This study sought to investigate the relationship between galectin-3 (Gal-3), myocardial fibrosis (MF) and outcomes in acute heart failure. Materials & methods: The single-nucleotide polymorphisms (SNPs) of LGALS3 at rs4644 and rs4652, plasma Gal-3 level, MF and major adverse events (MAEs) were obtained. Results: There was no significant difference in MAEs when categorizing patients by the LGALS3 SNPs at rs4644 and rs4652. The circulating Gal-3 was related to the degree of MF (p < 0.001). Plasma Gal-3 level and MF can predict an increased risk of MAEs (p < 0.001, p = 0.023, respectively). Conclusion: Not the SNPs of LGALS3 but Gal-3 and MF can predict MAEs in acute heart failure at 1 year of follow-up.

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Berry, William R., Christopher Michael Pieczonka, Nicholas J. Vogelzang, Lawrence Ivan Karsh, James L. Bailen, Krista Van Velzen, Harini Kandadi, Nadeem Anwar Sheikh, and Shaker R. Dakhil. "Antigen (Ag) spread after sipuleucel-T and correlation with overall survival (OS): A real-world experience." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e16504-e16504. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e16504.

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e16504 Background: Sipuleucel-T is an autologous cellular immunotherapy for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. In IMPACT (NCT00065442), a phase 3 trial, sipuleucel-T-induced immune responses against target Ag prostatic acid phosphatase (PAP) or PA2024, a recombinant protein consisting of PAP and granulocyte macrophage colony stimulating factor, correlated with OS (Sheikh 2013). Additionally, sipuleucel-T-induced immunoglobulin G (IgG) responses against secondary, non-target Ag (i.e. Ag spread) and the breadth of Ag spread also correlated with improved OS (GuhaThakurta 2015). Here we assessed Ag spread and OS in real-world patients from PRIME (NCT01727154), an immune monitoring sub-study of sipuleucel-T trials Methods: IgG levels in pre and wk 6 (2 wk post sipuleucel-T completion) sera from PRIME (n = 100) were quantified using Luminex xMAP. IgG responses to secondary Ag (LGALS3, PSA, KLK2, LGALS8, K-Ras, E-Ras) were defined as ≥ 1.5-fold increase over baseline. OS associations with individual Ag responses and total number of Ag per patient were assessed using the Kaplan-Meier method. Hazard ratios (HR) were estimated using a Cox Proportional Hazard Model. Results: IgG responses to ≥1 secondary Ag were observed in ≥72% of patients. Individual IgG responses to LGALS3, K-Ras, and LGALS8 at wk 6 were significantly associated with OS. Furthermore, breadth of Ag spread positively correlated with OS (Table); as the total number of Ag responses per patient increased, OS improved compared to patients with no secondary IgG responses. Conclusions: The results presented are consistent with findings from the prior phase 3 trial IMPACT. Secondary Ag responses were generated in real-world patients treated with sipuleucel-T, and these responses correlated with OS. Furthermore, breadth of Ag spread also correlated with improved OS. Clinical trial information: NCT01727154. [Table: see text]

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Jeftic, Ilija, Marina Miletic-Kovacevic, Nemanja Jovicic, Jelena Pantic, Nebojsa Arsenijevic, Miodrag L. Lukic, and Nada Pejnovic. "Galectin-3 Deletion Enhances Visceral Adipose Tissue Inflammation and Dysregulates Glucose Metabolism in Mice on a High-Fat Diet." Serbian Journal of Experimental and Clinical Research 17, no. 3 (September 1, 2016): 231–40. http://dx.doi.org/10.1515/sjecr-2016-0030.

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Abstract Obesity and type 2 diabetes mellitus (T2DM) constitute major health problems worldwide. Increased visceral adiposity enhances the risk of insulin resistance and type 2 diabetes. The mechanisms involved in obesity-associated chronic inflammation in metabolic tissues (metaflammation) that lead to insulin resistance and dysregulated glucose metabolism are incompletely defined. Galectin-3 (Gal-3), a β-galactoside-binding lectin, modulates immune/inflammatory responses and specifically binds to metabolic danger molecules. To dissect the role of Gal-3 in obesity and diabetes, Gal-3-deficient (LGALS3-/-) and wild-type (WT) C57Bl/6 male mice were placed on a high-fat diet (HFD, 60% kcal fat) or a standard chow diet (10% kcal fat) for 6 months and metabolic, histological and immunophenotypical analyses of the visceral adipose tissue were performed. HFD-fed LGALS3-/- mice had higher body weights and more body weight gain, visceral adipose tissue (VAT), hyperglycaemia, hyperinsulinemia, insulin resistance and hyperlipidemia than diet-matched WT mice. Compared to WT mice, the enlarged VAT in obese LGALS3-/- mice contained larger adipocytes. Additionally, we demonstrate enhanced inflammation in the VAT of LGALS3-/- mice compared with diet-matched WT mice. The VAT of LGALS3-/- mice fed a HFD contained more numerous dendritic cells and proinflammatory F4/80+CD11c+CD11b+ and F4/80high macrophages. In contrast to WT mice, the numbers of CXCR3+ and CD8+ T cells were increased in the VAT of Gal-3-deficient mice after 6 months of high-fat feeding. We provide evidence that Gal-3 ablation results in enhanced HFD-induced adiposity, inflammation in the adipose tissue, insulin resistance and hyperglycaemia. Thus, Gal-3 represents an important regulator of obesity-associated immunometabolic alterations.

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Kovacevic, Zoran, Tatjana Lazarevic, Nela Maksimovic, Milka Grk, Vladislav Volarevic, Marina Gazdic Jankovic, Svetlana Djukic, Katarina Janicijevic, Marina Miletic Kovacevic, and Biljana Ljujic. "Galectin 3 (LGALS3) Gene Polymorphisms Are Associated with Biochemical Parameters and Primary Disease in Patients with End-Stage Renal Disease in Serbian Population." Journal of Clinical Medicine 11, no. 13 (July 4, 2022): 3874. http://dx.doi.org/10.3390/jcm11133874.

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Galectin 3 plays a significant role in the development of chronic renal failure, particularly end-stage renal disease (ESRD). The aim of our study was to investigate the association between Gal-3 and biochemical parameters and primary disease in ESRD patients, by exploring the polymorphisms LGALS3 rs4644, rs4652, and rs11125. A total of 108 ESRD patients and 38 healthy controls were enrolled in the study. Genotyping of LGALS3 gene rs4644, rs4652, and rs11125 polymorphisms was performed by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). By multivariate logistic regression analysis, we found that LGALS3 rs4644 CC and rs4652 AA genotypes were significantly associated with a higher risk for lower hemoglobin, higher level of parathyroid hormone, and also occurrence of diabetes mellitus and arterial hypertension. The CAA haplotype was significantly more common in patients with diabetes, low hemoglobin level, and normal PTH level. It has been observed as well that the ACT haplotype was more common in patients with low glomerular filtration, low PTH, and normal hemoglobin level. We found that the LGALS3 rs4644 and rs4652 gene polymorphism may be involved in the pathogenesis and appearance of complications in ESRD patients and thus could be considered a new genetic risk factor in this population.

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Ó, Kleyton Palmeira do, Taciana Furtado de Mendonça-Belmont, Isabela Cristina Cordeiro Farias, Andreia Soares da Silva, Ana Karla da Silva Freire, Patrícia Muniz Mendes Freire de Moura, Luydson Richardson Silva Vasconcelos, et al. "LGALS3 +191A and +292C polymorphisms are associated with a reduction in serum gal-3 levels, but not with the clinical events of individuals with sickle cell anemia." Research, Society and Development 9, no. 9 (August 23, 2020): e442997314. http://dx.doi.org/10.33448/rsd-v9i9.7314.

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Objective: This study aimed to evaluate whether the single nucleotide polymorphisms (SNPs) +191 C>A (rs4644) and +292 A>C (rs4652) of the LGALS3 gene and the serum levels of galectin-3 (gal-3) are associated with clinical events in patients with sickle cell anemia (SCA). Methods: SNP +191 and +292 of the LGALS3 gene were detected by the TaqMan PCR system in real time. Gal-3 levels were measured in serum by ELISA. The study included 322 patients, mean age 36 (21-84). Results: AA and CA genotypes of the +191 region were related to lower levels of gal-3 when compared to CC genotype (p=0.0296). Lower level of gal-3 was also associated with the +191/+292 (AA/CC; CA/CC) diplotypes (p=0.0137) compared to the diplotypes (CC/AA; CC/CC; CC/AC; CA/AC). There was no association between serum levels of galectin-3 and genotype frequencies of the LGALS3 +191 and +292 polymorphisms with clinical events in SCA. Conclusion: The polymorphisms +191 and +292 of the LGALS3 are associated to decrease in serum levels of gal-3. However, no association of polymorphisms and levels of gal-3 with clinical events was observed in patients SCA.

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Darrow, April L., Ralph V. Shohet, and J. Gregory Maresh. "Transcriptional analysis of the endothelial response to diabetes reveals a role for galectin-3." Physiological Genomics 43, no. 20 (October 2011): 1144–52. http://dx.doi.org/10.1152/physiolgenomics.00035.2011.

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To characterize the endothelial dysfunction associated with Type II diabetes, we surveyed transcriptional responses in the vascular endothelia of mice receiving a diabetogenic, high-fat diet. Tie2-GFP mice were fed a diet containing 60% fat calories (HFD); controls were littermates fed normal chow. Following 4, 6, and 8 wk, aortic and leg muscle tissues were enzymatically dispersed, and endothelial cells were obtained by fluorescence-activated cell sorting. Relative mRNA abundance in HFD vs. control endothelia was measured with long-oligo microarrays; highly dysregulated genes were confirmed by real-time PCR and protein quantification. HFD mice were hyperglycemic by 2 wk and displayed vascular insulin resistance and decreased glucose tolerance by 5 and 6 wk, respectively. Endothelial transcripts upregulated by HFD included galectin-3 ( Lgals3), 5-lipoxygenase-activating protein, and chemokine ligands 8 and 9. Increased LGALS3 protein was detected in muscle endothelium by immunohistology accompanied by elevated LGALS3 in the serum of HFD mice. Our comprehensive analysis of the endothelial transcriptional response in a model of Type II diabetes reveals novel regulation of transcripts with roles in inflammation, insulin sensitivity, oxidative stress, and atherosclerosis. Increased endothelial expression and elevated humoral levels of LGALS3 supports a role for this molecule in the vascular response to diabetes, and its potential as a direct biomarker for the inflammatory state in diabetes.

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Qiu, H. F., X. W. Xu, S. H. Zhao, B. Fan, M. Yerle, and B. Liu. "Somatic cell hybrid and RH mapping of the porcine LGALS1, ITGA7, ITGB1, LGALS3, NOL12, GGA1, SH3BP1 and PDXP genes." Animal Genetics 38, no. 3 (June 2007): 315–16. http://dx.doi.org/10.1111/j.1365-2052.2007.01599.x.

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Petrylak, Daniel Peter, Emmanuel S. Antonarakis, Harini Kandadi, Lawrence Fong, Raymond S. Lance, Tuyen Vu, Nadeem Anwar Sheikh, Neal D. Shore, and Charles G. Drake. "The association of humoral antigen spread (AgS) with cytotoxic T lymphocyte (CTL) activity after sipuleucel-T (sip-T) treatment in two phase II clinical studies: STAMP and STRIDE." Journal of Clinical Oncology 38, no. 6_suppl (February 20, 2020): 112. http://dx.doi.org/10.1200/jco.2020.38.6_suppl.112.

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112 Background: Sip-T is an FDA-approved immunotherapy for metastatic castration-resistant prostate cancer. Sip-T generates CTL and humoral antigen activity, as measured by CD107a expression on PAP or PA2024 specific CD8+ T cells. These specific CTL activities were correlated with improved overall survival in several studies STAMP (NCT01487863) and STRIDE (NCT01981122) [1]. We examined whether CTL activity enables humoral response generation, hypothesizing that killing a target cell with immunotherapy releases antigens that generate a secondary antibody response, extending the effect. Methods: Using samples from patients who received sip-T in these studies, correlation between CTL activity and AgS responses to primary (PA2024, PAP) and secondary (PSA, LGALS3, LGALS8, KRAS, ERAS, KLK2) antibodies over time was assessed. Using R statistics software, a Wilcoxon signed rank test assessed differences across time (Wk, week: WK0, week 0, etc) and Spearman rank test for correlation between CTL activity and AgS responses. Results: In STAMP, PAP-specific CTL activity at WK0 was positively correlated with LGALS3 antibody responses at WK6, WK10, WK14 and WK26; likewise, PAP-specific CTL activity at WK6 was positively correlated with antibody response to PAP at WK0 (P = 0.035). In STRIDE, PAP-specific CTL activities at WK0 and both PAP- and PA2024-specific CTL activities at WK6 were positively correlated with LGALS8 antibody response at WK52. Plus, PAP- and PA2024- specific CTL activities at WK6 had significant, positive correlation with PA2024 antibody responses at WK0. In both, PA2024-specific CTL activity at WK26 was positively correlated with number of secondary antigen responses at WK10 and WK14. Conclusions: In all, PA2024-specific CTL activity at WK6 was positively correlated with antibody response to primary antigens (PA2024 and PAP) and 4 secondary antigens – PSA, KRAS, ERAS and KLK2 at multiple time points. In summary, treatment with sip-T in mCRPC appears to invoke the tumor immunity cycle, wherein tumor cell death releases compounds that act as secondary epitopes resulting in antigen spread. [1] DOI: 10.1158/1078-0432.CCR-18-0638. Clinical trial information: NCT01487863.

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Koh, Young Wha, Se Jin Jung, Chan-Sik Park, Dok Hyun Yoon, Cheolwon Suh, and Jooryung Huh. "LGALS3 as a prognostic factor for classical Hodgkin’s lymphoma." Modern Pathology 27, no. 10 (March 7, 2014): 1338–44. http://dx.doi.org/10.1038/modpathol.2014.38.

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Alencar, Gabriel F., Katherine M. Owsiany, Santosh Karnewar, Katyayani Sukhavasi, Giuseppe Mocci, Anh T. Nguyen, Corey M. Williams, et al. "Stem Cell Pluripotency Genes Klf4 and Oct4 Regulate Complex SMC Phenotypic Changes Critical in Late-Stage Atherosclerotic Lesion Pathogenesis." Circulation 142, no. 21 (November 24, 2020): 2045–59. http://dx.doi.org/10.1161/circulationaha.120.046672.

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Background: Rupture and erosion of advanced atherosclerotic lesions with a resultant myocardial infarction or stroke are the leading worldwide cause of death. However, we have a limited understanding of the identity, origin, and function of many cells that make up late-stage atherosclerotic lesions, as well as the mechanisms by which they control plaque stability. Methods: We conducted a comprehensive single-cell RNA sequencing of advanced human carotid endarterectomy samples and compared these with single-cell RNA sequencing from murine microdissected advanced atherosclerotic lesions with smooth muscle cell (SMC) and endothelial lineage tracing to survey all plaque cell types and rigorously determine their origin. We further used chromatin immunoprecipitation sequencing (ChIP-seq), bulk RNA sequencing, and an innovative dual lineage tracing mouse to understand the mechanism by which SMC phenotypic transitions affect lesion pathogenesis. Results: We provide evidence that SMC-specific Klf4- versus Oct4-knockout showed virtually opposite genomic signatures, and their putative target genes play an important role regulating SMC phenotypic changes. Single-cell RNA sequencing revealed remarkable similarity of transcriptomic clusters between mouse and human lesions and extensive plasticity of SMC- and endothelial cell-derived cells including 7 distinct clusters, most negative for traditional markers. In particular, SMC contributed to a Myh11 - , Lgals3 + population with a chondrocyte-like gene signature that was markedly reduced with SMC- Klf4 knockout. We observed that SMCs that activate Lgals3 compose up to two thirds of all SMC in lesions. However, initial activation of Lgals3 in these cells does not represent conversion to a terminally differentiated state, but rather represents transition of these cells to a unique stem cell marker gene–positive, extracellular matrix-remodeling, “pioneer” cell phenotype that is the first to invest within lesions and subsequently gives rise to at least 3 other SMC phenotypes within advanced lesions, including Klf4-dependent osteogenic phenotypes likely to contribute to plaque calcification and plaque destabilization. Conclusions: Taken together, these results provide evidence that SMC-derived cells within advanced mouse and human atherosclerotic lesions exhibit far greater phenotypic plasticity than generally believed, with Klf4 regulating transition to multiple phenotypes including Lgals3 + osteogenic cells likely to be detrimental for late-stage atherosclerosis plaque pathogenesis.

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Hartmann, Felicia, Daniel J. Gorski, Alexandra A. C. Newman, Susanne Homann, Anne Petz, Katherine M. Owsiany, Vlad Serbulea, et al. "SMC-Derived Hyaluronan Modulates Vascular SMC Phenotype in Murine Atherosclerosis." Circulation Research 129, no. 11 (November 12, 2021): 992–1005. http://dx.doi.org/10.1161/circresaha.120.318479.

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Rationale: Plaque instability remains poorly understood and new therapeutic approaches to reduce plaque rupture and subsequent clinical events are of great interest. Recent studies revealed an important role of phenotypic switching of smooth muscle cells (SMC) in controlling plaque stability, including ECM (extracellular matrix) deposition. Objective: The aim of this study was to elucidate the role of hyaluronan derived from SMC–hyaluronan synthase 3 ( Has3 ), in phenotypic switching and plaque stability in an animal model of atherosclerosis. Methods and Results: A mouse line with SMC-specific deletion of Has3 and simultaneous SMC-lineage tracing ( e YFP [enhanced yellow fluorescent protein]) on an Apoe −/− background was used. Lineage tracing of SMC with e YFP revealed that SMC-specific deletion of Has3 significantly increased the number of LGALS3 + (galectin-3) transition state SMC and decreased ACTA2 + (alpha-smooth muscle actin) SMC. Notably, SMC- Has3 deletion led to significantly increased collagen deposition and maturation within the fibrous cap and the whole lesion, as evidenced by picrosirius red staining and LC-PolScope analysis. Single-cell RNA sequencing of brachiocephalic artery lesions demonstrated that the loss of SMC- Has3 enhanced the transition of SMC to a Lgals3 + , ECM-producing phenotype with elevated acute-phase response gene expression. Experiments using cultured murine aortic SMC revealed that blocking CD44 (cluster of differentiation-44), an important hyaluronan binding receptor, recapitulated the enhanced acute-phase response, and synthesis of fibrous ECM. Conclusions: These studies provide evidence that the deletion of SMC- Has3 results in an ECM-producing transition state SMC phenotype (characterized by LGALS3 + expression), likely via reduced CD44 signaling, resulting in increased collagen formation and maturation, an index consistent with increased plaque stability.

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Kaur, Tarnjeet, Kshema Thakur, Jatinder Singh, Sukhdev Singh Kamboj, and Manpreet Kaur. "Identification of functional SNPs in human LGALS3 gene by in silico analyses." Egyptian Journal of Medical Human Genetics 18, no. 4 (October 2017): 321–28. http://dx.doi.org/10.1016/j.ejmhg.2017.02.001.

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Maupin, Kevin A., Daniel Dick, Johan Lee, and Bart O. Williams. "Loss of Lgals3 Protects Against Gonadectomy-Induced Cortical Bone Loss in Mice." Calcified Tissue International 106, no. 3 (November 19, 2019): 283–93. http://dx.doi.org/10.1007/s00223-019-00630-0.

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Ruberti, Samantha, Elisa Bianchi, Tiziana Fanelli, Sebastiano Rontauroli, Valentina Pennucci, Giuditta Corbizzi Fattori, Carmela Mannarelli, et al. "MAF Induces Inflammatory Mediators Involved in the Pathogenesis of Primary Myelofibrosis." Blood 128, no. 22 (December 2, 2016): 3132. http://dx.doi.org/10.1182/blood.v128.22.3132.3132.

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Abstract Primary Myelofibrosis (PMF) is a Philadelphia-negative myeloproliferative neoplasm characterized by the presence of hyperplastic/dysplastic megakaryocytes and the development of myelofibrosis and osteosclerosis. This disruption of the bone marrow (BM) structure results from a deregulated release of growth factors by malignant hematopoietic cells, particularly monocytes and megakaryocytes, that activate BM stromal cells (Desterke-C, Mediators Inflamm, 2015). Therefore, it remains of primary importance to identify novel therapeutic strategies to restore BM microenvironment homeostasis in PMF patients. In order to better characterize the molecular mechanisms underlying PMF pathogenesis, we have recently compared the gene expression profile (GEP) of CD34+ hematopoietic progenitor cells (HPCs) from PMF patients and healthy donors, and we observed the upregulation of the transcription factor MAF (v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog) (Norfo-R, Blood, 2014). With the aim to investigate the role of MAF in PMF pathogenesis and to reproduce the condition observed in PMF CD34+ cells, we studied the effects of MAF overexpression on HPCs differentiation. Human cord blood-derived CD34+ cells were transduced with a retroviral vector carrying the coding sequences for the two MAF transcript variants (LMAFVAR1IDN and LMAFVAR2IDN). The megakaryocyte lineage-committed CD41+ population was increased in LMAFVAR1IDN (38.2±2.3%) and LMAFVAR2IDN (39.4±2.3%) samples compared with the empty vector LXIDN (16.1±2.7%) at day 3 after NGFR+ cells purification. Values are reported as mean ± SEM from 3 independent experiments, p<.05. Moreover, MAF overexpression determined a remarkable increase of the CD14+ monocyte population in LMAFVAR1IDN (45.5±5.7%) and LMAFVAR2IDN (43.1±8.7%) compared to LXIDN control (8.0±0.4%) at t0 post-purification. Data represent mean ± SEM from 3 independent experiments, p<.05. Next, we analyzed the GEP of MAF-overexpressing CD34+ cells and observed the upregulation of genes involved in megakaryopoiesis, such as MERTK and RCAN1, and in monocyte/macrophage differentiation (e.g. EGR2 and KLF4). In particular, GEP revealed the upregulation of genes related to processes deregulated in PMF, such as fibrosis (i.e. ENPP2, ADAM9) and inflammation (i.e. TNF, CCL2 and CCL3). Noteworthy, several upregulated transcripts encoded for secreted proteins. Based on their role in inflammation and fibrosis, we selected a set of secreted molecules (IL8, MMP9, CCL2, SPP1, LGALS3 and PLAUR) and assessed them by quantitative enzyme-linked immunoassay (ELISA) in the culture supernatants from LMAFVAR1IDN-, LMAFVAR2IDN- and LXIDN-transduced cells. The levels in culture supernatants of all these molecules were increased in MAF-overexpressing samples compared to control. In order to correlate the expression of these molecules with MAF upregulation in PMF, we assessed them in plasma samples of PMF patients (n=30) and healthy donors (n=10). All the selected molecules displayed higher plasma levels in PMF patients than in healthy controls (Figure 1). Since the increase of SPP1 and LGALS3 has never been described before in PMF, we investigated which cell type could be responsible for SPP1 and LGALS3 production. Real Time qRTPCR performed on healthy donors peripheral blood-derived cells showed that the highest SPP1 expression levels were observed in CD34+ cells-derived megakaryocytes and granulocytes, whereas LGALS3 was expressed at higher levels in monocytes compared to the other cell types. Because the increased proliferation of fibroblasts is involved in BM fibrosis and is a PMF feature, we investigated the effects of LGALS3 and SPP1 on normal human primary dermal fibroblasts. The treatment with recombinant human LGALS3 (1000 ng/ml) or SPP1 (500 ng/ml) caused an increase in fibroblasts cell count of 20.9±2.7% (p<.001) and 14.9±4.1% (p<.01) compared to the untreated control, respectively. Values are reported as mean ± SEM from 7 independent experiments. Finally, we observed that increased SPP1 plasma levels in PMF patients correlate with a more severe fibrosis and lower overall survival (p<.05). In conclusion, our data unveil the involvement of MAF in PMF pathogenesis through the induction of a pro-fibrotic and pro-inflammatory phenotype in the malignant myeloid differentiated progeny. Disclosures Vannucchi: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

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Arar, Chantal, Jean-Charles Gaudin, Loı̈c Capron, and Alain Legrand. "Galectin-3 gene (LGALS3 ) expression in experimental atherosclerosis and cultured smooth muscle cells." FEBS Letters 430, no. 3 (July 3, 1998): 307–11. http://dx.doi.org/10.1016/s0014-5793(98)00683-8.

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Zhang, Shuxia, Yingru Xu, Chan Xie, Liangliang Ren, Geyan Wu, Meisongzhu Yang, Xingui Wu, et al. "RNF219/ α ‐Catenin/LGALS3 Axis Promotes Hepatocellular Carcinoma Bone Metastasis and Associated Skeletal Complications." Advanced Science 8, no. 16 (August 2021): 2102956. http://dx.doi.org/10.1002/advs.202102956.

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Wang, Hongxiang, Xiao Song, Qilin Huang, Tao Xu, Dapeng Yun, Yuqi Wang, Lingna Hu, et al. "LGALS3 Promotes Treatment Resistance in Glioblastoma and Is Associated with Tumor Risk and Prognosis." Cancer Epidemiology Biomarkers & Prevention 28, no. 4 (October 19, 2018): 760–69. http://dx.doi.org/10.1158/1055-9965.epi-18-0638.

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Krishna, Yamini, Amelia Acha-Sagredo, Dorota Sabat-Pośpiech, Natalie Kipling, Kim Clarke, Carlos R. Figueiredo, Helen Kalirai, and Sarah E. Coupland. "Transcriptome Profiling Reveals New Insights into the Immune Microenvironment and Upregulation of Novel Biomarkers in Metastatic Uveal Melanoma." Cancers 12, no. 10 (September 30, 2020): 2832. http://dx.doi.org/10.3390/cancers12102832.

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Metastatic uveal melanoma (mUM) to the liver is incurable. Transcriptome profiling of 40 formalin-fixed paraffin-embedded mUM liver resections and 6 control liver specimens was undertaken. mUMs were assessed for morphology, nuclear BAP1 (nBAP1) expression, and their tumour microenvironments (TME) using an “immunoscore” (absent/altered/high) for tumour-infiltrating lymphocytes (TILs) and macrophages (TAMs). Transcriptomes were compared between mUM and control liver; intersegmental and intratumoural analyses were also undertaken. Most mUM were epithelioid cell-type (75%), amelanotic (55%), and nBAP1-ve (70%). They had intermediate (68%) or absent (15%) immunoscores for TILs and intermediate (53%) or high (45%) immunoscores for TAMs. M2-TAMs were dominant in the mUM-TME, with upregulated expression of ANXA1, CD74, CXCR4, MIF, STAT3, PLA2G6, and TGFB1. Compared to control liver, mUM showed significant (p < 0.01) upregulation of 10 genes: DUSP4, PRAME, CD44, IRF4/MUM1, BCL2, CD146/MCAM/MUC18, IGF1R, PNMA1, MFGE8/lactadherin, and LGALS3/Galectin-3. Protein expression of DUSP4, CD44, IRF4, BCL-2, CD146, and IGF1R was validated in all mUMs, whereas protein expression of PRAME was validated in 10% cases; LGALS3 stained TAMs, and MFGEF8 highlighted bile ducts only. Intersegmental mUMs show differing transcriptomes, whereas those within a single mUM were similar. Our results show that M2-TAMs dominate mUM-TME with upregulation of genes contributing to immunosuppression. mUM significantly overexpress genes with targetable signalling pathways, and yet these may differ between intersegmental lesions.

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Yoshimura, Akinobu, Akihiko Gemma, Yoko Hosoya, Eriko Komaki, Yukio Hosomi, Tetsuya Okano, Kiyosi Takenaka, et al. "Increased expression of the LGALS3 (Galectin 3) gene in human non–small-cell lung cancer." Genes, Chromosomes and Cancer 37, no. 2 (June 2003): 159–64. http://dx.doi.org/10.1002/gcc.10205.

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Raimond, J., D. B. Zimonjic, C. Mignon, M. G. Mattei, N. C. Popescu, M. Monsigny, and A. Legrand. "Mapping of the galectin-3 gene (LGALS3) to human Chromosome 14 at region 14q21-22." Mammalian Genome 8, no. 9 (September 1997): 706–7. http://dx.doi.org/10.1007/s003359900548.

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Takashima, Yasuo, Atsushi Kawaguchi, Azusa Hayano, and Ryuya Yamanaka. "CD276 and the gene signature composed of GATA3 and LGALS3 enable prognosis prediction of glioblastoma multiforme." PLOS ONE 14, no. 5 (May 10, 2019): e0216825. http://dx.doi.org/10.1371/journal.pone.0216825.

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Azevedo Foinquinos, Gabriela, Maria Eduarda Azevedo Acioli, Antônio Henrique Santana Cavalcanti, Walter Lins Barbosa Junior, Raul Emídio Lima, Norma Thomé Juca, Rosa Cirne de Azevedo Foinquinos, et al. "Influence of LGALS3 and PNPLA3 genes in non-alcoholic steatohepatitis (NASH) in patients undergone bariatric surgery." Obesity Research & Clinical Practice 14, no. 4 (July 2020): 326–32. http://dx.doi.org/10.1016/j.orcp.2020.07.004.

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Hu, Chung-Yi, Sheng-Kai Chang, Chien-Sheng Wu, Wei-I. Tsai, and Ping-Ning Hsu. "Galectin-3 gene (LGALS3) +292C allele is a genetic predisposition factor for rheumatoid arthritis in Taiwan." Clinical Rheumatology 30, no. 9 (April 8, 2011): 1227–33. http://dx.doi.org/10.1007/s10067-011-1741-2.

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Chattopadhyay, Pratip K., Guo-Jian Gao, Ian Taylor, Kayla Guidry, Kristin Labbe, Christina Almonte, Margaret Nakamoto, and Kwok Kin-Wong. "Molecular cytometry identifies a wide range of translationally relevant markers in tumor and peripheral immune cells of lung cancer patients." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 242.30. http://dx.doi.org/10.4049/jimmunol.204.supp.242.30.

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Abstract Many immunotherapy drugs, used singly or in combination, are emerging. To realize precision oncology, and better design clinical trials, in-depth immune profiling is key. Many new technologies are available; the most promising simultaneously analyzes >102 proteins and 400 mRNA cell-by-cell (molecular cytometry). Using this technology, we deeply profiled TIL, from freshly resected lung tissue, and PBMC collected at surgery (n=10). Antibody staining was robust, with all canonical cell populations at expected frequency. We identified markers uniquely upregulated in TIL, including CXCR6, CD39, CD26, CD69, CD103, and RGS. We also asked what markers were uniquely enriched in PD1-TIL, in order to find other drug targets for patients who fail Nivolumab. We found many molecules upregulated in PD1-TIL, including CD326, CD98, LGALS3, TIM3, CD54, CD235ab, CXCL8, CD141, and CD117. We further identified precise combinations of these markers that inform design of combination immunotherapy. We also characterized immune landscapes in metastatic disease vs. localized adenocarcinoma, finding drug targets and tumor-immune interactions are different across these settings. For example, T-cell activation markers are downregulated in metastatic tissue, e.g., HLADR (p = 1.5E-16), CD69 (p=2.9e-10), and CD38 (p=3.2e-16). CD103 was also highly downregulated (p=1.9E-14). Notably, in metastatic disease various myeloid proteins are elevated, including CD206 (p=0.002), CD32 (p=0.02), and CD61 (p=0.006). We also characterized the degree of immune exhaustion, using ratios of ZBED2:LGALS in cells. In summary, we demonstrate the utility of molecular cytometry for providing unique (and translationally-relevant) insight into lung cancer.

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Furuya, Tatiane K., Carlos E. Jacob, Michele T. P. Tomitão, Lizeth C. C. Camacho, Marcus F. K. P. Ramos, José Eluf-Neto, Venâncio A. F. Alves, et al. "Association between Polymorphisms in Inflammatory Response-Related Genes and the Susceptibility, Progression and Prognosis of the Diffuse Histological Subtype of Gastric Cancer." Genes 9, no. 12 (December 13, 2018): 631. http://dx.doi.org/10.3390/genes9120631.

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The chronic inflammatory microenvironment and immune cell dysfunction have been described as critical components for gastric tumor initiation and progression. The diffuse subtype is related to poor clinical outcomes, pronounced inflammation, and the worst prognosis. We investigated the association of polymorphisms in inflammatory response-related genes (COX-2, OGG1, TNFB, TNFA, HSPA1L, HSPA1B, VEGFA, IL17F, LGALS3, PHB, and TP53) with gastric cancer susceptibility, progression and prognosis in a Brazilian sample, focusing on the diffuse subtype. We also performed the analysis regarding the total sample of cases (not stratified for tumor subtypes), allowing the comparison between the findings. We further investigated the polymorphisms in linkage disequilibrium and performed haplotype association analyses. In the case-control study, rs1042522 (TP53) was associated with a stronger risk for developing gastric cancer in the sample stratified for diffuse subtype patients when compared to the risk observed for the total cases; CTC haplotype (rs699947/rs833061/rs2010963 VEGFA) was associated with risk while rs699947 was associated with protection for gastric malignancy in the total sample. Regarding the associations with the clinicopathological features of gastric cancer, for the diffuse subtype we found that rs699947 and rs833061 (VEGFA) were associated with outcomes related to a worse progression while rs5275 (COX-2), rs909253 (TNFB), and rs2227956 (HSPA1L) were associated to a better progression of the disease. In the total sample, rs699947 and rs833061 (VEGFA), rs4644 (LGALS3), and rs1042522 (TP53) were able to predict a worse progression while rs5275 (COX-2), rs2227956 (HSPA1L), and rs3025039 (VEGFA) a better progression. Besides, rs909253 (TNFB) predicted protection for the overall and disease-free survivals for gastric cancer. In conclusion, these results helped us to clarify the potential role of these polymorphisms in genes involved in the modulation of the inflammatory response in the pathogenesis of gastric cancer.

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Rong, Jingjing, Hongwei Pan, Jin He, Yu Zhang, Yongjun Hu, Changlu Wang, Qinghua Fu, et al. "Long non-coding RNA KCNQ1OT1/microRNA-204-5p/LGALS3 axis regulates myocardial ischemia/reperfusion injury in mice." Cellular Signalling 66 (February 2020): 109441. http://dx.doi.org/10.1016/j.cellsig.2019.109441.

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Wang, Yan, Maryamsadat Seyedsadr, and Silva Markovic-Plese. "Single-cell RNA sequence (scRNAseq) analysis of T regulatory cells in relapsing remitting multiple sclerosis (RRMS)." Journal of Immunology 208, no. 1_Supplement (May 1, 2022): 162.13. http://dx.doi.org/10.4049/jimmunol.208.supp.162.13.

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Abstract Patients with RRMS have decreased numbers and function of Tregs, which may play a causative role in the pathogenesis of the disease. Here, we used scRNAseq to define Tregs populations in peripheral blood of 3 RRMS patients and 3 matched healthy controls (HCs) and compare their transcriptomes and function. We clustered sorted CD4+CD25+CD127− Tregs into active (a) and resting (r)Tregs. Our initial scRNAseq data analysis of the active Tregs identified 324 up-regulated differentially expressed genes (DEGs) and 208 down-regulated genes in RRMS in comparison to HCs. Upregulated genes include major histocompatibility complex (MHC) class I (HLAA, HLAB) and class II (HLADRB5) and TRCA gene, supportive of their activated status; ICAM2, involved in the migration to the CNS; ID3, involved in maintaining Treg pool and suppressive function; LAIR2, an indicator for exhaustive Tregs; NEAT1, whose silencing promotes Treg/Th17 balance, and TCF7, that limits Treg thymic generation. Genes with decreased expression include CD7, required for Treg homeostasis; costimulatory CD81; CTLA4 and JUNB required for optimal Treg function; IFTM1 and IF16 that may regulate IFN type I induction of Tregs; CXCR4; LGALS1 and LGALS3 coding for galectin 1 and 3 which inhibit Treg function; and NFKBIA and TNFAIP3, all suggestive of decreased Treg function in RRMS. Pathway enrichment analysis for DEGs in RRMS Tregs identified the strongest enrichment for type I IFN signaling pathway. Understanding the transcriptional changes involved in deficient Tregs functions in RRMS is crucial for better understanding of the disease pathogenesis and for a development of effective treatment for this disabling disease. State of Pennsylvania grant: Deficient T regulatory Cell (Treg) Function in Relapsing Remitting Multiple Sclerosis (RRMS)

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Jee, Hyeon-Gun, Byoung-Ae Kim, Minjun Kim, Hyeong Yu, June Choi, Su-jin Kim, and Kyu Lee. "Expression of SLC5A5 in Circulating Tumor Cells May Distinguish Follicular Thyroid Carcinomas from Adenomas: Implications for Blood-Based Preoperative Diagnosis." Journal of Clinical Medicine 8, no. 2 (February 18, 2019): 257. http://dx.doi.org/10.3390/jcm8020257.

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Preoperative diagnosis of thyroid nodules reduces unnecessary surgery. Circulating tumor cells (CTCs) may contain information of primary tumor(s). We asked whether the peripheral blood expression of genes specific for circulating tumor cells (CTCs) differentiates benign thyroid nodules from malignant nodules. Peripheral blood mononuclear cells from thyroid nodule patients (n = 20) were isolated preoperatively and the expression of seven CTC-associated genes was measured in patients with thyroid nodule(s) (n = 20). Among the tested genes, the expression of SLC5A5 and LGALS3 were validated in a larger number of patients (n = 64) and our results show that SLC5A5 expression differentiated follicular adenomas from follicular carcinomas (area under the curve (AUC) = 0.831). The expression of SLC5A5 in CTCs may preoperatively distinguish thyroid follicular adenomas from follicular carcinomas.

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Knights, Alexander J., Jinfen J. Yik, Hanapi Mat Jusoh, Laura J. Norton, Alister P. W. Funnell, Richard C. M. Pearson, Kim S. Bell-Anderson, Merlin Crossley, and Kate G. R. Quinlan. "Krüppel-like Factor 3 (KLF3/BKLF) Is Required for Widespread Repression of the Inflammatory Modulator Galectin-3 (Lgals3)." Journal of Biological Chemistry 291, no. 31 (May 24, 2016): 16048–58. http://dx.doi.org/10.1074/jbc.m116.715748.

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Zhang, Yuhui, Yunhong Wang, Mei Zhai, Tianyi Gan, Xuemei Zhao, Rongcheng Zhang, Tao An, Yan Huang, Qiong Zhou, and Jian Zhang. "Influence of LGALS3 gene polymorphisms on susceptibility and prognosis of dilated cardiomyopathy in a Northern Han Chinese population." Gene 642 (February 2018): 293–98. http://dx.doi.org/10.1016/j.gene.2017.11.026.

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Welle, S., S. Welt, T. Shay, C. Lanning, K. Horton, and D. Kostyal. "The use of gene array analysis to determine down-stream molecular expression patterns of trastuzumab (T) treatment." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 14135. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.14135.

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14135 Background: Breast cancers expressing the HER/2 amplicon are more aggressive and are associated with a poorer prognosis. HER/2 over-expression has been correlated with expression of proteins responsible for invasion, metastases, rapid growth, angiogenesis and apoptosis. However, it is unknown if T treatment of HER/2 over-expressing tumors reverses these phenotypes. Methods: BT 474 and SK-BR3 breast cancer cell lines contain the HER/2 amplicon. Under growth conditions demonstrating inhibitory effects of T by MTT and 3H-Thymidine incorporation, (0.25–50 micrograms/ml for up to 9 days), RNA extracts from treated and un- treated cells were analyzed and compared by whole human genome, gene array analysis. Results: Specific gene products reported to be up-regulated in HER/2 over-expressed breast cancer lines or responsible for aggressive behavior were assessed for down regulation by T treatment including: topoisomerase II, heregulin, egfr-1,2,3 and 4, p27, ki67, mapKinase, akt, caspase-3, caspase-7, caspase-9, bcl-2, veg-f, veg-f receptor, p38, sapk/jnk, erk1/2, LGALS1 galectin-1, LGALS3 galectin-3, proline-4-hydrolase P4HA2, FN1 fibronectin -1, CDH3 p-cadherin, laminin receptor protein -1, pro2605 and insulin like growth factor binding protein-3. No significant change in these mRNA levels were observed due to T treatment. In contrast, over 1000 other gene were found to be specifically and significantly up or down regulated including the down regulation of S100 Calcium binding protein associated with increase metastatic potential. Conclusions T treatment does not reverse the expression of a large array of proteins conferring poor prognostic features on HER/2+ tumor. The use of gene array analysis to study T induced gene expression is a robust method to assess downstream protein expression patterns mediated by antibody binding to receptor. No significant financial relationships to disclose.

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HAN, LU, ZHIXIONG WU, and QICHENG ZHAO. "Revealing the molecular mechanism of colorectal cancer by establishing LGALS3-related protein-protein interaction network and identifying signaling pathways." International Journal of Molecular Medicine 33, no. 3 (January 8, 2014): 581–88. http://dx.doi.org/10.3892/ijmm.2014.1620.

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Karger, S., K. Krause, M. Gutknecht, K. Schierle, D. Graf, F. Steinert, H. Dralle, and D. Führer. "ADM3, TFF3 and LGALS3 are discriminative molecular markers in fine-needle aspiration biopsies of benign and malignant thyroid tumours." British Journal of Cancer 106, no. 3 (January 2012): 562–68. http://dx.doi.org/10.1038/bjc.2011.578.

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Ocklenburg, Frank, Darius Moharregh-Khiabani, Robert Geffers, Viktoria Janke, Susanne Pfoertner, Henk Garritsen, Lothar Groebe, et al. "UBD, a downstream element of FOXP3, allows the identification of LGALS3, a new marker of human regulatory T cells." Laboratory Investigation 86, no. 7 (May 15, 2006): 724–37. http://dx.doi.org/10.1038/labinvest.3700432.

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Lan, M., T. Xu, D. R. Gomez, M. D. Jeter, Q. N. Nguyen, W. Deng, S. H. Lin, R. U. Komaki, and Z. Liao. "Association Between LGALS3 Gene Polymorphisms and Survival in Non–Small Cell Lung Cancer Patients Treated With Definitive Radiation Therapy." International Journal of Radiation Oncology*Biology*Physics 98, no. 1 (May 2017): 249–50. http://dx.doi.org/10.1016/j.ijrobp.2017.01.196.

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Polishchuk, T. V. "Plasma levels of galectin-3 in residents of the Podillya region of Ukraine without signs of cardiovascular pathology carriers of different variants of the coding gene (LGALS-3, rs 2274273)." Reports of Vinnytsia National Medical University 26, no. 4 (December 24, 2022): 540–44. http://dx.doi.org/10.31393/reports-vnmedical-2022-26(4)-03.

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Annotation. The purpose of the study is to investigate the plasma level of galectin-3 in postmenopausal women without signs of cardiovascular pathology and its possible association with the structural and functional parameters of the myocardium in carriers of different polymorphic variants of the coding gene (LGALS-3, rs2274273). 67 women of postmenopausal age (average age 56.43±0.64 years) without signs of cardiovascular pathology residents of the Podillya region of Ukraine were examined. In addition to the general clinical examination, the research used the enzyme immunoassay method to determine the level of galectin-3 in blood plasma, genotyping of the LGALS3 gene at the rs2274273 locus by means of polymerase chain reaction, and ultrasound of the heart. Statistical processing of the obtained results was carried out using the package of statistical programs SPSS, STATISTICA v. 10.0. By means of correlation analysis with the calculation of Spearman's rank correlation coefficients (r), an assessment of the possible association of the plasma level of the biomarker and the structural and functional indicators of the heart was carried out. The critical value of the significance level (p) was ≤0.05. In the examined population of women, there was no significant difference between the frequency of occurrence of the GA and GG genotypes carriers of the galectin-3 gene locus rs2274273: 49.25% (n=33) and 40.30% (n=27), respectively (p>0.05). The AA genotype variant was found in 10.45% (n=7) of individuals, which is significantly less frequent than both the GA and GG genotypes (p<0.01). The frequency of distribution of genotypes corresponded to the Hardy-Weinberg equilibrium. The average level of galletin-3 in blood plasma in women was 6.68±0.30 ng/ml, it was within the generally accepted norms and did not reliably differ from the corresponding indicators in men of the same region. No significant difference in plasma concentrations of galectin-3 was found in carriers of different polymorphic variants of the galectin-3 gene. Correlation between the level of galectin-3 in the blood plasma and most indicators of intracardiac and systemic hemodynamics in women without cardiovascular pathology was not found. In the future, it is planned to study the formation of prerequisites for chronic heart failure (CHF) in women with EH based on indicators of the plasma level of galectin-3 in carriers of polymorphic variants of the coding gene (LGALS-3, rs2274273).

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Fong, Lawrence, Eric Jay Small, Daniel Peter Petrylak, David I. Quinn, Emmanuel S. Antonarakis, Adam S. Kibel, Nancy N. Chang, Harini Kandadi, Nadeem Anwar Sheikh, and Charles G. Drake. "Antigen spread (AgS) after sipuleucel-T (sip-T): A cross-trial comparison of 4 sip-T clinical trials of patients (pts) with prostate cancer (PC)." Journal of Clinical Oncology 35, no. 6_suppl (February 20, 2017): 143. http://dx.doi.org/10.1200/jco.2017.35.6_suppl.143.

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143 Background: Sip-T, an FDA-approved autologous immunotherapy for pts with asymptomatic or minimally symptomatic metastatic castration-resistant PC (mCRPC), is manufactured from peripheral blood mononuclear cells cultured with PA2024, a fusion antigen of prostatic acid phosphatase (PAP) conjugated to granulocyte macrophage colony-stimulating factor. In sip-T–treated pts, antibody responses to PA2024/PAP (target antigens) and AgS (antibody responses to secondary [2°] antigens) correlate with improved OS (Sheikh 2013; GuhaThakurta 2015). We assessed if a greater magnitude of AgS would be observed in an earlier PC disease stage when the immune system is more intact. Methods: Pt serum was from 1 non-metastatic, androgen-dependent PC (ADPC) sip-T trial (STAND, sip-T + androgen deprivation, NCT01431391) and 3 mCRPC sip-T trials (IMPACT, sip-T vs control, NCT00065442; STAMP, sip-T + abiraterone acetate, NCT01487863; STRIDE, sip-T + enzalutamide, NCT01981122). Using a Luminex assay, mean fold-change in IgG responses to target and 2° cancer-related antigens (PSA, LGALS3, LGALS8, ERAS, KRAS, KLK2) was evaluated from baseline to wk 6. Results: AgS was evaluated in 308 pts. The mean fold-change in IgG responses to target antigens was greater for ADPC vs mCRPC pts (p < 0.01). Moreover, the magnitude of IgG responses was greater for most 2° antigens in ADPC vs mCRPC pts (p < 0.05; Table), except for PSA and KLK2 in ADPC vs STRIDE pts. Conclusions: The magnitude ofantibody responses to target and 2° antigens was greater earlier in the PC disease course, consistent with increased antigen-presenting cell activation in ADPC vs mCRPC pts. Increased AgS likely reflects stronger sip-T–induced immune responses, previously associated with extended OS in mCRPC (Sheikh 2013; GuhaThakurta 2015). Future research is warranted on the clinical benefit of sip-T earlier in the PC disease course and the potential impact of androgen suppression on the magnitude of AgS and outcomes. Clinical trial information: NCT01431391; NCT00065442; NCT01487863; NCT01981122. [Table: see text]

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Lee, Jongwon, Jungmin Choi, and In Hae Park. "Abstract P5-02-51: Single-cell transcriptome reveals distinct peripheral blood immune landscapes associated with sensitivity to anti-HER2 treatment in HER2-positive metastatic breast cancer patients." Cancer Research 83, no. 5_Supplement (March 1, 2023): P5–02–51—P5–02–51. http://dx.doi.org/10.1158/1538-7445.sabcs22-p5-02-51.

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Abstract Background: Different immune cell states reflect distinct tumor microenvironment and led to various clinical outcomes for cancer patients. However, very few studies examined the contribution of peripheral blood (PB) immune landscapes to the treatment response due to the limited applications. This study aimed to explore the circulating immune cell landscapes associated the sensitivity to cytotoxic chemotherapy with trastuzumab in HER2 positive metastatic breast cancer patients. Methods: Whole blood were drawn at baseline and after 2 cycles of trastuzumab plus cytotoxic chemotherapy from six patients (3 responders and 3 non-responders). Approximately 3,500 to 10,000 peripheral blood mononuclear cells per patients were profiled using single-cell RNA sequencing (scRNA-seq). scRNA-seq data were further processed and analyzed using Seurat package version 3.1. Cell populations were clustered using the Louvain algorithm and subsequently annotated using known marker genes. Differential abundance in cell population was quantified using MiloR and differentially expressed genes were detected using MAST between responders and non-responders. Results: After removing low quality cells, a total of 65,295 cells were clustered into 18 clusters. CD8 Effector T, CD4 Naïve T, CD4 Effector T, Cytotoxic NK, Naïve B, Plasma B and Monocytes were significantly enriched in responders compared to non-responders. Especially, CD8 Effector T, NK, Plasma B and Classical Monocytes showed distinct patterns that those cells were enriched in pre-treatment than post-treatment of responder but not in non-responder. From the differentially expressed gene analysis, cytotoxic or costimulatory marker genes (GZMK, GZMA, GNLY, CCL5, NKG7, PRF1) were enriched in responders. While, exhausted or coinhibitory marker genes (DNAJB1, LGALS9, HAVCR2) were enriched in non-responders. Gene set enrichment analysis revealed four pathways associated with T cell, B cell receptor signaling, NK cell mediated cytotoxicity and Cytokine-cytokine receptor interaction which showed differences between responders and non-responders following chemotherapy. Finally, validation with flow cytometry using independent cohort showed that constant expression manner in HAVCR2, LGALS9 and LGALS3 genes. Conclusions: Single-cell transcriptome analysis identified distinct PB immune landscapes associated with treatment response in HER2-positive metastatic breast cancer patients. Differential abundance and unique gene expression programs of immune cell populations could serve as potential predictive biomarkers for anti-HER2 therapy. Citation Format: Jongwon Lee, Jungmin Choi, In Hae Park. Single-cell transcriptome reveals distinct peripheral blood immune landscapes associated with sensitivity to anti-HER2 treatment in HER2-positive metastatic breast cancer patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-02-51.

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Ruvolo, Peter P., Chenyue W. Hu, Yihua Qiu, Vivian R. Ruvolo, Robin L. Go, Stefan E. Hubner, Kevin R. Coombes, Michael Andreeff, Amina A. Qutub, and Steven M. Kornblau. "LGALS3 is connected to CD74 in a previously unknown protein network that is associated with poor survival in patients with AML." EBioMedicine 44 (June 2019): 126–37. http://dx.doi.org/10.1016/j.ebiom.2019.05.025.

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Journal articles on the topic 'LGALS3'

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