Background
Galectin-1 (encoded by LGALS1) is a β-galactoside–binding lectin with well-established roles in immune regulation, angiogenesis, and extracellular matrix remodeling. Although its oncogenic and immunomodulatory functions have been described in individual tumor entities, a systematic evaluation of Galectin-1 across human cancers that integrates multiple molecular layers and the tumor microenvironment has been lacking.
Objectives
To perform a comprehensive multi-omics pan-cancer analysis of Galectin-1 in order to characterize its expression, epigenetic regulation, prognostic relevance, and association with immune and stromal features across diverse malignancies.
Methods
We conducted a large-scale multi-omics pan-cancer analysis using exclusively open-access, publicly available datasets, primarily from The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC). The study integrated RNA-seq, proteomics, DNA methylation, and harmonized clinical data across more than 30 cancer types, encompassing more than a thousand tumor samples alone or matched normal tissues. Differential expression between tumor and normal tissues was assessed at both transcript and protein levels, and promoter methylation was evaluated using Illumina array data. Prognostic associations were examined using Cox regression and Kaplan–Meier analyses. To contextualize Galectin-1 within the tumor microenvironment, immune and stromal cell infiltration were inferred using established deconvolution approaches, complemented by immunophenoscore metrics. Differential gene expression analyses comparing high versus low LGALS1 tumors were conducted within each cancer type, followed by functional enrichment and pathway-level association analyses. To contextualize Galectin-1 within the tumor microenvironment, immune and stromal cell infiltration were inferred using established deconvolution approaches, complemented by immunophenoscore metrics. Differential gene expression analyses comparing high versus low LGALS1 tumors were conducted within each cancer type, followed by functional enrichment and pathway-level association analyses.
Results
LGALS1 expression was significantly upregulated in multiple cancers at both RNA and protein levels, frequently accompanied by promoter hypomethylation. Elevated Galectin-1 expression was associated with poorer overall survival in several tumor types, whereas higher promoter methylation generally correlated with more favorable outcomes. Transcriptomic comparisons consistently revealed enrichment of biological processes related to extracellular matrix organization, epithelial–mesenchymal transition, angiogenesis, and stromal activation in tumors with high LGALS1 expression. Immune analyses showed positive associations with myeloid populations, including macrophages and dendritic cells, together with reduced CD8? T-cell infiltration in selected cancers. Stromal deconvolution further demonstrated increased fibroblast and endothelial cell abundance in Galectin-1–high tumors. At the pathway level, Galectin-1 protein abundance was strongly linked to epithelial–mesenchymal transition, TGF-β signaling, and hypoxia-related programs across multiple malignancies.
Conclusions
Leveraging large, globally accessible cancer genomics resources, this multi-omics pan-cancer study identifies Galectin-1 as a recurrently dysregulated molecule across human cancers, with consistent associations to adverse prognosis and a stromal-activated, immunosuppressive tumor microenvironment. By relying entirely on population-scale open datasets, our findings underscore the value of public cancer resources for generating globally relevant biological insights. Collectively, the results support LGALS1 as a promising biomarker of tumor aggressiveness and a potential therapeutic target, particularly in cancers characterized by immune evasion and extensive matrix remodeling.