In:
Frontiers in Pharmacology, Frontiers Media SA, Vol. 15 ( 2024-7-22)
Abstract:
Background: Glucagon-like peptide-1 (GLP-1) has crucial impact on glycemic control and weight loss physiologically. GLP-1 receptor agonists have been approved for treatment of diabetes and obesity. Emerging evidence suggests that GLP-1 receptor agonists exert anticancer effect in tumorigenesis and development. However, the role and mechanism of GLP-1 signaling-related genes in pan-cancer still need further study. Methods: We comprehensively investigated the aberrant expression and genetic alterations of GLP-1 signaling-related genes in 33 cancer types. Next, GLP-1 signaling score of each patient in The Cancer Genome Atlas were established by the single-sample gene set enrichment analysis. In addition, we explored the association of GLP-1 signaling score with prognostic significance and immune characteristics. Furthermore, qRT-PCR and immunohistochemistry staining were applied to verify the expression profiling of GLP-1 signaling-related genes in colorectal cancer (CRC) tissues. Wound-healing assays and migration assays were carried out to validate the role of GLP-1 receptor agonist in CRC cell lines. Results: The expression profiling of GLP-1 signaling-related genes is commonly altered in pan-cancer. The score was decreased in cancer tissues compared with normal tissues and the lower expression score was associated with worse survival in most of cancer types. Notably, GLP-1 signaling score was strongly correlated with immune cell infiltration, including T cells, neutrophils, dendritic cells and macrophages. In addition, GLP-1 signaling score exhibited close association with tumor mutation burden, microsatellite instability and immunotherapy response in patients with cancer. Moreover, we found that the expression of GLP-1 signaling-related genes ITPR1 and ADCY5 were significantly reduced in CRC tissues, and GLP-1 receptor agonist semaglutide impaired the migration capacity of CRC cells, indicating its protective role. Conclusion: This study provided a preliminary understanding of the GLP-1 signaling-related genes in pan-cancer, showing the prognosis significance and potential immunotherapeutic values in most cancer types, and verified the potential anticancer effect of GLP-1 receptor agonist in CRC.
Type of Medium:
Online Resource
ISSN:
1663-9812
DOI:
10.3389/fphar.2024.1387243
DOI:
10.3389/fphar.2024.1387243.s001
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2024
detail.hit.zdb_id:
2587355-6
SSG:
15,3
