Abstract
BACKGROUND: Ovarian cancer (OC) is a highly aggressive gynecological malignancy, with a poor 5-year survival rate of less than 50%. Identifying novel biomarkers and therapeutic targets is crucial to improving patient prognosis. Sortilin-related VPS10 domain-containing receptor 2 (SORCS2) regulates various biological processes and is implicated in carcinogenesis, yet its specific role in OC remains unclear. MATERIALS AND METHODS: Multiple bio-informatics analyses were used to analyze SORCS2 expression and potential role in OC. Cell proliferation, migration assays and flow cytometry were performed to assess the effects of SORCS2 on OC cells. Further, Xenograft mouse models were built to identify its function in OC cell growth in vivo. RESULTS: In this study, we first identified that SORCS2 expression is down-regulated in OC tissues, correlating with adverse clinical characteristics and poor clinical outcomes, emphasizing its potential as a prognostic marker for OC. In vitro, SORCS2 over-expression suppressed cell proliferation and migration, induced cell cycle arrest at the S/G2 phase via the p21/CCNA1 pathway, and induced apoptosis by regulating PIDD1 and CASP9. Xenograft mouse models further validated the tumor-suppressive effects of SORCS2 in vivo. Additionally, SORCS2 was found to participate in tumor-specific immune responses by promoting T cell activation and release of immune factors. CONCLUSION: Our findings underscore SORCS2 as a tumor suppressor in OC development and highlight its potential as a prognostic marker for OC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-025-01822-z.