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

Abstract

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.

Keywords: GPX4; SLC7A11; ferroptosis; ovarian cancer; platinum resistance; poor prognosis.