Diagnostic and prognostic value of RUNX1 in ovarian serous cystadenocarcinoma and its role in cancer progression via suppressing ferroptosis

Abstract Introduction We explore the clinical and prognostic significance of RUNX1 in ovarian serous cystadenocarcinoma (OSC) and report its previously unreported role in regulating ferroptosis. Materials and Methods RUNX1 expression and prognosis were tested using TCGA-OV and GTEx data. Functional roles were assessed in vitro via RUNX1 knockdown in OSC cell lines, while measuring proliferation (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and colony formation) and ferroptosis sensitivity (erastin treatment and glutathione/malondialdehyde (GSH/MDA) assays). Mechanisms were explored via western blotting and bioinformatic analysis. Results RUNX1 was significantly higher in OSC patients and correlated to poor overall survival, thereby indicating its prognostic value. RUNX1 knockdown suppressed proliferation and increased erastin-induced ferroptosis sensitivity. Silencing RUNX1 reduced GSH, elevated MDA, and inhibited Nrf2 signaling, thus, suggesting ferroptosis regulation via this pathway. Conclusion RUNX1 is an independent prognostic biomarker for OSC. Crucially, we provide novel evidence that RUNX1 promotes OSC progression by conferring resistance to ferroptosis likely through the Nrf2 pathway. Thus, targeting the RUNX1-ferroptosis axis represents a promising therapeutic strategy.