Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece.
Clinical Research Unit, Department of Obstetrics and Gynecology, School of Medicine, Technical University of Munich, Munich, Germany.
Int J Cancer. 2020 Dec 15;147(12):3560-3573. doi: 10.1002/ijc.33182. Epub 2020 Aug 1.
Ovarian cancer (OC) remains a leading cause of gynecological cancer-related death worldwide, characterized by poor 5-year survival. Molecular markers could serve as crucial tools of personalized prognosis and therapy. Herein, we present miR-181a as novel predictor of OC prognosis, using five independent OC cohorts. In particular, a screening (n = 81) and an institutionally independent validation (n = 100, OVCAD multicenter study) serous OC (SOC) cohorts were analyzed. Bagnoli et al (2016) OC179 (n = 124) to OC133 (n = 100) and TCGA (n = 489) served as external validation cohorts. Patients' survival and disease progression were assessed as clinical endpoint events. Bootstrap analysis was performed for internal validation and decision curve analysis was utilized to evaluate clinical benefit. miR-181a overexpression was unveiled as powerful and independent molecular predictor of patients' poor survival and higher risk for disease progression after debulking surgery and platinum-based chemotherapy. Analysis of the OVCAD institutionally independent cohort, as well as of Bagnoli et al. and TCGA external cohorts further confirmed the unfavorable prognostic nature of miR-181a overexpression in SOC. Strikingly, multivariate prognostic models incorporating miR-181a with established disease markers clearly improved patients' risk-stratification and offered superior clinical benefit in OC prognostication. Conclusively, miR-181a evaluation could augment prognostic accuracy and support precision medicine decisions in OC.
卵巢癌(OC)仍然是全球妇科癌症相关死亡的主要原因,其 5 年生存率较差。分子标志物可以作为个性化预后和治疗的重要工具。在此,我们使用五个独立的 OC 队列展示了 miR-181a 作为 OC 预后的新型预测因子。特别是,分析了筛选(n=81)和机构独立验证(n=100,OVCAD 多中心研究)浆液性 OC(SOC)队列。Bagnoli 等人(2016 年)OC179(n=124)至 OC133(n=100)和 TCGA(n=489)作为外部验证队列。将患者的生存和疾病进展作为临床终点事件进行评估。进行了 bootstrap 分析以进行内部验证,并利用决策曲线分析来评估临床获益。miR-181a 的过表达被揭示为患者不良生存和在减瘤手术后和铂类化疗后疾病进展风险更高的强大且独立的分子预测因子。对 OVCAD 机构独立队列以及 Bagnoli 等人和 TCGA 外部队列的分析进一步证实了 miR-181a 过表达在 SOC 中的不良预后性质。引人注目的是,包含 miR-181a 与既定疾病标志物的多变量预后模型明显改善了患者的风险分层,并在 OC 预后预测中提供了更高的临床获益。总之,miR-181a 的评估可以提高预后准确性,并为 OC 中的精准医学决策提供支持。