Screening of differentially methylated genes in breast cancer and risk model construction based on TCGA database.
Screening of differentially methylated genes in breast cancer and risk model construction based on TCGA database.
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DOI：
10.3892/ol.2018.9457
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发表时间：
2018-11
期刊：
影响因子：
2.9
通讯作者：
Jin F
中科院分区：
文献类型：
--
作者：
Feng L;Jin F
筛选出乳腺癌差异甲基化基因，构建乳腺癌预后风险模型。从The Cancer Genome Atlas（TCGA）下载乳腺癌相关水平3的RNA-seq数据和甲基化数据，并使用MethylMix R软件包筛选癌组织和正常组织中差异甲基化的基因。应用大卫分析差异甲基化基因的GO富集，应用ApproximusPathDB分析差异甲基化基因的PATHWAY通路，应用单因素、多因素考克斯分析和Akaike信息准则（AIC）构建乳腺癌预后风险模型，应用ROC曲线判断风险模型的临床应用价值。在癌组织和正常组织中成功筛选出257个差异甲基化基因，其中39个与GO富集相关，19个与PATHWAY通路相关;获得最佳预后风险模型，风险评分= QRFP（甲基化程度）×（−3.657）+ S100A16 ×（−3.378）+TDRD 1 ×（−4.001）+ SMO ×（3.548）;从每个样本中确定风险评分的中值为0.936;以其为界值，高危组5年生存率为72.4%（95% CI，62.7-83.6%），低危组为86.6%（95% CI，78.6-95.3%）。高危组与低危组的生存率差异有显著性（P<0.001）。ROC曲线的AUC为0.791，该模型具有较好的临床应用价值。本研究成功发现多个乳腺癌相关甲基化基因，分析它们与乳腺癌病程及预后的关系。此外，还构建了一个预后风险模型，为进一步研究甲基化在乳腺癌发生发展中的作用提供了基础。
Differentially methylated genes in breast cancer were screened out and a prognostic risk model of breast cancer was constructed. RNA-seq data and methylation data for breast cancer-related level 3 were downloaded from The Cancer Genome Atlas (TCGA), and MethylMix R package was used to screen out differentially methylated genes in cancer tissues and normal tissues. DAVID was used to analyze the GO enrichment of differentially methylated genes, ConsensusPathDB to analyze the PATHWAY pathways of differentially methylated genes, the single factor, multivariate Cox analysis and Akaike Information Criterion (AIC) to construct the prognostic risk model of breast cancer, and the ROC curve to judge the clinical application value of the risk model. Two hundred and fifty-seven differentially methylated genes were successfully screened out in cancer tissues and normal tissues; 39 related to GO enrichments and 19 related to PATHWAY pathways were found; the best prognostic risk model was obtained, risk score = QRFP (degree of methylation) × (−3.657) + S100A16 × (−3.378) + TDRD1 × (−4.001) + SMO × (3.548); it was determined from each sample that the median value of the risk score was 0.936; using it as the cut-off value, the five-year survival rate in high-risk group of patients was 72.4% (95% CI, 62.7–83.6%), and that in low-risk group of patients was 86.6% (95% CI, 78.6–95.3%). The difference in the survival rate between the high-risk and low-risk groups was significant (P<0.001). The AUC of ROC curve was 0.791, so the model had a good clinical application value. This study successfully found multiple breast cancer-related methylation genes, the relationship between them and the course and prognosis of breast cancer was analyzed. Moreover, a prognostic risk model was constructed, which facilitated the expansion of the current study on the role of methylation in the occurrence and development of breast cancer.
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影响因子：
5.7
作者：
Kakizaki F;Sonoshita M;Miyoshi H;Itatani Y;Ito S;Kawada K;Sakai Y;Taketo MM
通讯作者：
Taketo MM
影响因子：
11.2
作者：
Abu Aboud O;Habib SL;Trott J;Stewart B;Liang S;Chaudhari AJ;Sutcliffe J;Weiss RH
通讯作者：
Weiss RH
影响因子：
5.7
作者：
Udali S;Guarini P;Ruzzenente A;Ferrarini A;Guglielmi A;Lotto V;Tononi P;Pattini P;Moruzzi S;Campagnaro T;Conci S;Olivieri O;Corrocher R;Delledonne M;Choi SW;Friso S
通讯作者：
Friso S
影响因子：
2.9
作者：
Zuo TT;Zheng RS;Zeng HM;Zhang SW;Chen WQ
通讯作者：
Chen WQ
影响因子：
30.8
作者：
Weinstein, John N.;Collisson, Eric A.;Mills, Gordon B.;Shaw, Kenna R. Mills;Ozenberger, Brad A.;Ellrott, Kyle;Shmulevich, Ilya;Sander, Chris;Stuart, Joshua M.
通讯作者：
Stuart, Joshua M.