Zhang Jin, Yang Lixiao, Xiang Xiaohong, Li Zhuoying, Qu Kai, Li Ke
Department of Clinical Laboratory, Liaocheng People's Hospital, Taishan Medical College, Liaocheng, Shandong Province 252000, China.
Department of Obstetrics and Gynecology, Liaocheng People's Hospital, Taishan Medical College, Liaocheng, Shandong Province 252000, China.
Aging (Albany NY). 2018 Jun 17;10(6):1366-1379. doi: 10.18632/aging.101473.
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, and . 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.
卵巢癌是所有致死性妇科癌症中死亡率最高的，其预后并不理想，主要障碍在于对化疗的耐药性。肿瘤组织中活性氧（ROS）的产生通过介导细胞寿命与化疗效果相关。在本研究中，我们筛选了接受铂类化疗的卵巢癌患者中氧化应激相关基因的预后价值，并构建了一个由三个基因组成的预后基因特征。在训练队列（n = 276）和验证队列（n = 230）中，这个三基因特征均与总生存期（OS）显著相关，但与无进展生存期（PFS）无关。有趣的是，我们发现三基因特征在铂敏感患者中的预后价值得到增强。亚组分析进一步表明，低风险评分组中年龄较大、病理分级较高和肿瘤分期较晚的患者可从铂类化疗中获益。功能分析表明，包括细胞周期、胰岛素样生长因子1（IGF1）/mTOR和Fas通路在内的几个信号通路的失活受到这三个基因的影响。总体而言，我们的结果提供了证据，表明一组三个氧化应激相关基因特征对接受铂类化疗的卵巢癌患者具有预后价值。
