Department of Reproductive Genetics, International Peace Maternity and Child Health Hospital, Shanghai Key Laboratory of Embryo Original Diseases, Shanghai Municipal Key Clinical Specialty, Shanghai Jiao Tong University School of Medicine, No.910, Hengshan Road, Shanghai, 200030, People's Republic of China.
Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, China.
J Ovarian Res. 2021 Mar 6;14(1):41. doi: 10.1186/s13048-021-00791-3.
Existing clinical methods for prognosis evaluating for Epithelial Ovarian Cancer (EOC) patients had defects of invasive, unsystematic and subjective and little data are available for individualizing treatment, therefore, to identify potential prognostic markers and new therapeutic targets for EOC is urgently required.
Expression of 232 autophagy-related genes (ARGs) in 354 EOC and 56 human ovarian surface epithelial specimens from 7 independent laboratories were analyzed, 31 mRNAs were identified as DEARGs. We did functional and pathway enrichment analysis and constructed protein-protein interaction network for all DEARGs. To screen out candidate DEARGs related to EOC patients' survival and construct an autophagy-related prognostic risk signature, univariate and multivariate Cox proportional hazards models were established separately. Finally, 5 optimal independent prognostic DEARGs (PEX3, DNAJB9, RB1, HSP90AB1 and CXCR4) were confirmed and the autophagy-related risk model was established by the 5 prognostic DEARGs. The accuracy and robustness of the prognostic risk model for survival prediction were evaluated and verified by analyzing the correlation between EOC patients' survival status, clinicopathological features and risk scores.
The autophagy-related prognostic risk model can be independently used to predict overall survival in EOC patients, it can also potentially assist in individualizing treatment and biomarker development.
现有的上皮性卵巢癌(EOC)患者预后评估临床方法存在侵入性、非系统性和主观性缺陷,且缺乏个体化治疗的数据,因此,迫切需要鉴定 EOC 的潜在预后标志物和新的治疗靶点。
分析了 7 个独立实验室的 354 例 EOC 和 56 例人卵巢表面上皮标本中 232 个自噬相关基因(ARGs)的表达,鉴定出 31 个差异表达的 ARGs(DEARGs)。我们对所有 DEARGs 进行了功能和通路富集分析,并构建了蛋白-蛋白相互作用网络。为了筛选出与 EOC 患者生存相关的候选 DEARGs,并构建自噬相关的预后风险特征,我们分别建立了单变量和多变量 Cox 比例风险模型。最后,确认了 5 个最佳独立预后 DEARGs(PEX3、DNAJB9、RB1、HSP90AB1 和 CXCR4),并通过这 5 个预后 DEARGs 构建了自噬相关的风险模型。通过分析 EOC 患者的生存状态、临床病理特征和风险评分之间的相关性,评估和验证了预后风险模型对生存预测的准确性和稳健性。
自噬相关的预后风险模型可独立用于预测 EOC 患者的总生存期,还可能有助于个体化治疗和生物标志物的开发。