Abstract
Ovarian cancer yields the highest mortality rate of all lethal gynecologic cancers, and the prognosis is unsatisfactory with the major obstacle in resistance to chemotherapy. The generation of reactive oxygen species (ROS) in tumor tissues was associated with chemotherapeutic effectiveness by mediating cellular longevity. In this study, we screened the prognostic values of oxidative stress-related genes in ovarian cancer patients received platinum-based chemotherapy, and conducted a prognostic gene signature composing of three genes, TXNRD1, GLA and GSTZ1. This three-gene signature was significantly associated with overall survival (OS), but not progression-free survival (PFS), in both training (n=276) and validation cohorts (n=230). Interestingly, we found that the prognostic value of three-gene signature was reinforced in platinum-sensitive patients. Subgroup analysis further suggested that patients with elder age, higher pathological grades and advanced tumor stages in low-risk score group could benefit from platinum-based chemotherapy. Functional analysis showed that the inactivation of several signaling pathways, including cell cycle, insulin-like growth factor 1 (IGF1) /mTOR and Fas pathways, was affected by three genes. Collectively, our results provided evidence that a panel of three oxidative stress-related gene signature had prognostic values for ovarian cancer patients received platinum-based chemotherapy.