LGALS1 promotes gastric cancer progression and is associated with epithelial-mesenchymal transition and tumor immune microenvironment features

Galectin-1 (Gal-1, encoded by LGALS1) has been implicated in malignant progression across multiple cancer types, but its prognostic significance and association with tumor immune microenvironment features in gastric cancer (GC) remain incompletely understood. In this study, we integrated data from The Cancer Genome Atlas and Gene Expression Omnibus databases with in vitro functional assays, a nude-mouse xenograft model, transcriptomic profiling, and miRNA-related analyses to investigate the clinical and biological relevance of LGALS1 in GC. LGALS1 was significantly overexpressed in gastric tumor tissues and was associated with unfavorable patient prognosis. In TCGA-STAD, LGALS1 expression was negatively correlated with tumor mutational burden and microsatellite instability, while showing positive associations with ESTIMATE-derived immune/stromal scores, suggesting a potential link between LGALS1 and an immune- and stroma-rich tumor context. These immune-related findings are based on computational analyses and require further spatial and functional validation. Further analysis showed that LGALS1 expression was correlated with EMT-related markers, including CDH1 and CDH2, suggesting that LGALS1 dysregulation may be associated with EMT-related molecular changes. Our experiments showed that LGALS1 overexpression enhanced GC cell proliferation, migration, and invasion, while a nude-mouse xenograft model showed that LGALS1 overexpression promoted tumor growth in vivo. Additionally, hsa-miR-22-3p was downregulated in GC tissues and inversely associated with LGALS1 expression. Pharmacological inhibition of LGALS1 with OTX008 attenuated the increase in colony formation induced by hsa-miR-22-3p inhibition, supporting a Gal-1-related contribution to this phenotype. Together with previous evidence that miR-22 can directly regulate galectin-1 in other tumor contexts, these findings suggest a potential hsa-miR-22-3p/LGALS1 regulatory relationship in GC. Overall, our results support LGALS1 as a candidate prognostic biomarker and potential therapeutic target in GC, while the direct miRNA-targeting relationship, immune-regulatory mechanisms, and causal role of EMT require further validation.