Identification of prognosis markers for endometrial cancer by integrated analysis of DNA methylation and RNA-Seq data
Identification of prognosis markers for endometrial cancer by integrated analysis of DNA methylation and RNA-Seq data
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DOI：
10.1038/s41598-019-46195-8
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发表时间：
2019-07-09
影响因子：
4.6
通讯作者：
Shen, Keng
中科院分区：
文献类型：
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作者：
Huo, Xiao;Sun, Hengzi;Shen, Keng
子宫内膜癌恶性程度高，晚期预后差，因此预测其预后非常重要。DNA甲基化作为用于各种癌症的诊断、预后和预测目的的生物标志物已迅速获得临床关注。本研究根据DNA甲基化和RNA-Seq数据，鉴定差异甲基化位点和差异表达基因。通过功能分析和相互作用网络来识别枢纽基因，并验证枢纽基因的总生存分析。通过子宫内膜癌组织的免疫组织化学染色来评估前几个基因。通过基因敲除子宫内膜癌细胞系CDC 20和CCNA 2后的细胞生长曲线评价基因功能。共鉴定出329个低甲基化的高表达基因和359个高甲基化的低表达基因，根据互作网络得到4个枢纽基因。CDC 20和CCNA 2低表达的患者总体生存率较好。免疫组化染色也证实了这一结果。细胞生长曲线也表明，敲低CDC 20和CCNA 2可以抑制细胞增殖。我们已经确定了两个异常甲基化的基因，CDC 20和CCNA 2作为精确诊断EC的新生物标志物。
Endometrial cancer is highly malignant and has a poor prognosis in the advanced stage, thus, prediction of its prognosis is important. DNA methylation has rapidly gained clinical attention as a biomarker for diagnostic, prognostic and predictive purposes in various cancers. In present study, differentially methylated positions and differentially expressed genes were identified according to DNA methylation and RNA-Seq data. Functional analyses and interaction network were performed to identify hub genes, and overall survival analysis of hub genes were validated. The top genes were evaluated by immunohistochemical staining of endometrial cancer tissues. The gene function was evaluated by cell growth curve after knockdown CDC20 and CCNA2 of endometrial cancer cell line. A total of 329 hypomethylated highly expressed genes and 359 hypermethylated lowly expressed genes were identified, and four hub genes were obtained according to the interaction network. Patients with low expression of CDC20 and CCNA2 showed better overall survival. The results also were demonstrated by the immunohistochemical staining. Cell growth curve also demonstrated that knockdown CDC20 and CCNA2 can suppress the cell proliferation. We have identified two aberrantly methylated genes, CDC20 and CCNA2 as novel biomarkers for precision diagnosis in EC.