Abstract
BACKGROUND: Gallbladder cancer (GBC) is a highly aggressive malignancy of the biliary tract. It often lacks distinct symptoms in its early stages, and no specific biomarkers have yet been identified for its diagnosis. OBJECTIVE: To identify key genes involved in GBC pathogenesis using public databases and bioinformatics analysis and validate these findings experimentally, providing a foundation for developing potential GBC biomarkers. METHODS: Analysis of GBC-related data from the Gene Expression Omnibus database revealed that G protein-coupled receptor 64 (GPR64) was differentially expressed in GBC. GPR64 expression in GBC-SD and NOZ cells was modulated using lentiviral transfection. Functional assays assessed cancer-related phenotypes, while apoptosis was measured using flow cytometry. Xenograft models in nude mice were established with cell lines overexpressing GPR64. RESULTS: GPR64 expression was reduced in GBC. Its overexpression suppressed GBC cell invasion, migration, and proliferation, and induced apoptosis. In vivo findings were consistent with in vitro results. CONCLUSION: GPR64 plays a critical role in GBC pathogenesis and may serve as a promising biomarker for its diagnosis and treatment.