Zhang Zhe, Huang Ke, Gu Chenglei, Zhao Luyang, Wang Nan, Wang Xiaolei, Zhao Dongsheng, Zhang Chenggang, Lu Yiming, Meng Yuanguang
Department of Gynecologic Oncology, Chinese PLA General Hospital, Beijing 100853, China.
Beijing Institute of Health Service and Medical Information, Beijing 100850, China.
Sci Rep. 2016 May 17;6:26001. doi: 10.1038/srep26001.
Classification of ovarian cancer by morphologic features has a limited effect on serous ovarian cancer (SOC) treatment and prognosis. Here, we proposed a new system for SOC subtyping based on the molecular categories from the Cancer Genome Atlas project. We analyzed the DNA methylation, protein, microRNA, and gene expression of 1203 samples from 599 serous ovarian cancer patients. These samples were divided into nine subtypes based on RNA-seq data, and each subtype was found to be associated with the activation and/or suppression of the following four biological processes: immunoactivity, hormone metabolic, mesenchymal development and the MAPK signaling pathway. We also identified four DNA methylation, two protein expression, six microRNA sequencing and four pathway subtypes. By integrating the subtyping results across different omics platforms, we found that most RNA-seq subtypes overlapped with one or two subtypes from other omics data. Our study sheds light on the molecular mechanisms of SOC and provides a new perspective for the more accurate stratification of its subtypes.
根据形态学特征对卵巢癌进行分类,对浆液性卵巢癌(SOC)的治疗和预后影响有限。在此,我们基于癌症基因组图谱项目的分子类别,提出了一种新的SOC亚型分类系统。我们分析了599例浆液性卵巢癌患者的1203份样本的DNA甲基化、蛋白质、微小RNA和基因表达情况。这些样本根据RNA测序数据被分为九个亚型,并且发现每个亚型都与以下四个生物学过程的激活和/或抑制相关:免疫活性、激素代谢、间充质发育和丝裂原活化蛋白激酶(MAPK)信号通路。我们还鉴定出了四种DNA甲基化、两种蛋白质表达、六种微小RNA测序和四种通路亚型。通过整合不同组学平台的亚型分类结果,我们发现大多数RNA测序亚型与来自其他组学数据的一到两个亚型重叠。我们的研究揭示了SOC的分子机制,并为其亚型更准确的分层提供了新的视角。