High Co-Expression of GPAT4 and SLC7A11 as a Predictor of Platinum Resistance and Poor Prognosis in Patients with Epithelial Ovarian Cancer

TL;DR

High levels of GPAT4 and SLC7A11 in ovarian cancer are linked to platinum resistance and worse survival, suggesting new treatment strategies.

Contribution

Identifies GPAT4 and SLC7A11 co-expression as a novel predictor of platinum resistance and poor prognosis in ovarian cancer.

Findings

High GPAT4 and SLC7A11 expression is associated with platinum resistance in ovarian cancer tissues.

Combined high expression of GPAT4 and SLC7A11 is an independent predictor of poor overall survival.

Inhibitors of GPAT4 and SLC7A11, when combined with cisplatin, improve chemotherapeutic effects in resistant cancer cells.

Abstract

Background/Objectives: This study aimed to determine whether the expression levels of GPAT4 and SLC7A11 are associated with survival outcomes and platinum resistance in epithelial ovarian cancer (EOC) patients. Methods: We analyzed the medical records of EOC patients. EOC samples obtained during surgery were stained for GPAT4 and SLC7A11. Cox regression and Kaplan—Meier analyses were performed to assess the impact of GPAT4 and SLC7A11 expression on overall survival (OS). Results: We found that GPAT4 and SLC7A11 expression levels were greater in platinum-resistant ovarian cancer tissues than in platinum-sensitive ovarian cancer tissues. High expression of both GPAT4 and SLC7A11 was associated with an increased risk of platinum resistance compared with low expression of both factors. High expression of both SLC7A11 and GPAT4 was independently correlated with poor OS, highlighting the significance of this integrated metric as a prognostic factor in ovarian cancer. The GPAT inhibitor (GPAT-IN-1) and an SLC7A11 inhibitor (erastin) attenuated platinum resistance in ovarian cancer cells, and their combined application increased cytotoxicity. Furthermore, the combination of GPAT-IN-1, erastin, and cisplatin significantly improved the chemotherapeutic effects on platinum-resistant ovarian cancer cells. Conclusions: High expression of both SLC7A11 and GPAT4 is related to platinum resistance in EOC patients. The high expression of both SLC7A11 and GPAT4 serves as an important independent prognostic factor and indicates potential therapeutic targets for patients with platinum-resistant EOC.

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