Expression and functional diversity of the glucagon-like peptide-1 receptor across tumor types.

PURPOSE: Glucagon-like peptide-1 receptor (GLP-1R) agonists are widely used to treat type 2 diabetes mellitus (T2DM) and obesity. Emerging evidence suggests potential links between GLP-1R signaling and cancer risk or progression, but its role in tumor biology remains unclear. This study investigated GLP-1R expression and prognostic value across multiple cancer types using large-scale genomic datasets.

METHODS

We analyzed GLP-1R mRNA expression using data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and the Human Protein Atlas. Expression patterns in tumors were compared to normal tissues, including samples from rapid autopsies. Survival analyses were conducted across cancer types, and GLP-1R gene alterations were assessed via cBioPortal.

RESULTS

GLP-1R expression showed marked variation across cancers. It was lower in breast, lung, and colon cancers, but elevated in esophageal, kidney, and thyroid tumors compared to normal tissues. Higher GLP-1R expression correlated with improved overall survival in low-grade glioma but with worse outcomes in lung squamous cell carcinoma. Patterns of disease-free survival varied similarly. Genetic alterations in GLP-1R were rare, with amplifications most common, particularly in esophageal and ovarian cancers.

CONCLUSION

GLP-1R shows tissue-specific expression and prognostic relevance across cancer types. The low expression of GLP-1R across cancer types and the low frequency of genetic alterations suggest a limited direct role of GLP-1R mutations in cancer progression, but its variable expression may influence tumor behavior. Further research is needed to clarify both the functional role of GLP-1R in cancer biology and the safety and therapeutic potential of GLP-1R agonists in oncology.