Analysis of the proliferative role and prognostic value of GPR173 in gastric cancer.

BACKGROUND: Gastric cancer (GC) is a leading cause of cancer-related death with a poor prognosis, highlighting an urgent need for novel therapeutic targets and biomarkers. The function of G protein-coupled receptor 173 (GPR173), an orphan receptor, remains unknown in GC. This study aimed to comprehensively characterize the clinical significance and biological function of GPR173 in GC. METHODS: We analyzed GPR173 expression and its prognostic value using data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and an in-house clinical cohort (consisting of 136 gastric cancer patients) via immunohistochemistry. The biological functions of GPR173 were investigated through in vitro gain- and loss-of-function assays (CCK-8, colony formation, EdU) and an in vivo xenograft model. The underlying molecular mechanism was explored using bioinformatics, Western blotting, and immunofluorescence. RESULTS: GPR173 was upregulated in GC tissues across TCGA, GEO, and internal cohorts (all P < 0.01), correlating with advanced T (P = 0.016) and N stages (P = 0.002). Multivariate analysis identified high GPR173 as an independent prognostic factor in both the TCGA (HR = 1.33, P = 0.0076) and our clinical cohort (HR = 2.35, P = 0.014). Functionally, GPR173 promoted cell proliferation in vitro and tumor growth in vivo (P < 0.001). Mechanistically, GPR173 activated PI3K/AKT signaling, and the AKT inhibitor MK-2206 reversed these oncogenic effects. CONCLUSION: Our findings establish GPR173 as a novel oncogene in gastric cancer that promotes tumor progression through activation of the PI3K/AKT pathway. GPR173 serves as a robust prognostic biomarker for poor patient survival, representing a potential new therapeutic target for GC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12957-026-04274-x.