Choi J, Ye S, Eng K H, Korthauer K, Bradley W H, Rader J S, Kendziorski C
University of Wisconsin Madison, Madison, WI, USA.
Medical College of Wisconsin, Milwaukee, WI, USA.
Stat Biosci. 2017 Jun;9(1):1-12. doi: 10.1007/s12561-016-9144-1. Epub 2016 Mar 29.
Despite improvements in operative management and therapies, overall survival rates in advanced ovarian cancer have remained largely unchanged over the past three decades. Although it is possible to identify high-risk patients following surgery, the knowledge does not provide information about the genomic aberrations conferring risk, or the implications for treatment. To address these challenges, we developed an integrative pathway-index model and applied it to messenger RNA expression from 458 patients with serous ovarian carcinoma from the Cancer Genome Atlas project. The biomarker derived from this approach, IPI59, contains 59 genes from six pathways. As we demonstrate using independent datasets from six studies, IPI59 is strongly associated with overall and progression-free survival, and also identifies high-risk patients who may benefit from enhanced adjuvant therapy.
尽管手术管理和治疗方法有所改进,但在过去三十年中,晚期卵巢癌的总体生存率基本保持不变。虽然术后有可能识别出高危患者,但这一信息并未提供关于导致风险的基因组畸变或其对治疗影响的信息。为应对这些挑战,我们开发了一种综合通路指数模型,并将其应用于来自癌症基因组图谱项目的458例浆液性卵巢癌患者的信使核糖核酸表达。通过这种方法得出的生物标志物IPI59包含来自六个通路的59个基因。正如我们使用六项研究的独立数据集所证明的那样,IPI59与总生存期和无进展生存期密切相关,还能识别出可能从强化辅助治疗中获益的高危患者。