Expression and functional diversity of the glucagon-like peptide-1 receptor across tumor types
Mario M Alba1,2, Wilson H Lee1, Jerry S H Lee3,4,5,6
1Department of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy, University of Southern California, Los Angeles, CA, USA.
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.
Insights
Glucagon-like peptide-1 receptor (GLP-1R) expression varies by cancer type, impacting patient outcomes. While GLP-1R mutations are rare, its expression may influence tumor behavior, warranting further oncology research.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Glucagon-like peptide-1 receptor (GLP-1R) agonists are established treatments for type 2 diabetes mellitus (T2DM) and obesity.
- Emerging evidence suggests a potential connection between GLP-1R signaling and cancer development or progression.
- The precise role of GLP-1R in tumor biology remains incompletely understood.
Purpose of the Study:
- To investigate the expression patterns of GLP-1R across various human cancer types.
- To determine the prognostic significance of GLP-1R expression in different cancers.
- To analyze the frequency and types of genetic alterations in the GLP-1R gene within tumors.
Main Methods:
- Utilized large-scale genomic datasets from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and the Human Protein Atlas.
- Compared GLP-1R mRNA expression levels in tumor tissues versus adjacent normal tissues.
- Performed survival analyses (overall and disease-free) and assessed GLP-1R genetic alterations using cBioPortal.
Main Results:
- GLP-1R expression exhibited significant heterogeneity across cancer types, being lower in breast, lung, and colon cancers, but higher in esophageal, kidney, and thyroid tumors.
- Elevated GLP-1R expression correlated with improved survival in low-grade glioma but poorer outcomes in lung squamous cell carcinoma.
- Genetic alterations in GLP-1R were infrequent, with amplifications observed most notably in esophageal and ovarian cancers.
Conclusions:
- GLP-1R demonstrates tissue-specific expression and possesses prognostic value in diverse cancer types.
- The low incidence of GLP-1R genetic alterations suggests a limited direct role of mutations in cancer progression.
- Variable GLP-1R expression may influence tumor behavior, necessitating further investigation into its functional role and the therapeutic potential of GLP-1R agonists in oncology.
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