High co‐expression of SLC7A11 and GPX4 as a predictor of platinum resistance and poor prognosis in patients with epithelial ovarian cancer

OBJECTIVE: The aim was to assess the expression levels of SLC7A11 and GPX4 in relation to platinum resistance and prognosis in patients with epithelial ovarian cancer (EOC). DESIGN: A retrospective cohort study. SETTING: Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China. POPULATION OR SAMPLE: We included 192 eligible patients from hospital between January 2002 and December 2018. METHODS: We retrospectively analysed the medical records of patients with EOC. Surgical specimens of EOC were stained for SLC7A11 and GPX4. Survival analysis was performed using the Kaplan–Meier and Cox regression methods. MAIN OUTCOME MEASURES: Clinical end points include platinum‐free interval (PFI), progression‐free survival (PFS) and overall survival (OS). RESULTS: Patients with high co‐expression levels of SLC7A11 and GPX4 had a 60‐fold higher risk of platinum resistance compared with those with low co‐expression (risk ratio, 60.46; 95% confidence interval [CI] 22.76–160.58; p < 0.001). Moreover, high co‐expression level of SLC7A11 and GPX4 was an independent prognostic factor for poor OS (p < 0.001, hazard ratio [HR] 4.44, 95% CI, 2.77–7.14) and poor PFS (p < 0.001, HR = 5.73, 95% CI, 3.86–8.73). For in vitro experiments, SLC7A11 and GPX4 expression were both upregulated in platinum‐resistant cells compared with their parental ovarian cancer cells, and siRNA‐induced SLC7A11 and GPX4 inhibition decreased platinum resistance. CONCLUSIONS: High expression levels of SLC7A11 and GPX4 are associated with platinum resistance in EOC patients. High co‐expression of SLC7A11 and GPX4 may be a significant independent prognostic factor and a potential therapeutic target for platinum resistance in EOC patients.