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

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. 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. 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. 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.