Li Kaixue, Zeng Li, Wei Hong, Hu Jingjing, Jiao Lu, Zhang Juan, Xiong Ying
Department of Gastroenterology, The Second People's Hospital of Shenzhen, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China.
Department of Gastroenterology, The Second People's Hospital of Shenzhen, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China.
Cancer Genet. 2018 Dec;228-229:5-11. doi: 10.1016/j.cancergen.2018.05.003. Epub 2018 May 26.
Colorectal Cancer (CC), a common disease causing approximately million deaths annually, has been the third most frequent type of malignancy. We aimed to identify gene-specific DNA methylation signature to function as prognostic and predictive markers for CC patient survival.
Expression profiles of gene-specific DNA methylation and the corresponding clinical information of 201 CC patients were downloaded from The Cancer Genome Atlas (TCGA) dataset and differentially expressed gene-specific DNA methylation was identified after tumor subtype classification. A risk score model was further built by analyzing the expression data of these gene-specific DNA methylations from the training dataset of CC patients.
Totally, 214 gene-specific DNA methylations were found to be expressed significantly between different subtypes of CC, including 150 up-regulated and 64 down-regulated ones. Up-regulated gene-specific DNA methylation accounted for 70.1% and the down-regulated gene-specific DNA methylation accounted for 29.9%. Hereinto, six gene-specific DNA methylations were obtained, including methy_vimentin and methy_ TFPI2, which were found significantly correlated with overall survival status of patients with CC.
With the six gene-specific DNA methylation signatures, patients in the training set were divided into low-risk and high- risk groups. What's more, gene-specific DNA methylation target genes were highly associated with protein phosphorylation, which indicated that further research on phosphorylation of target gene-coding protein might provide new sight on the treatment of CC.
结直肠癌（CC）是一种常见疾病，每年导致约百万例死亡，已成为第三大常见恶性肿瘤类型。我们旨在鉴定基因特异性DNA甲基化特征，以作为CC患者生存的预后和预测标志物。
从癌症基因组图谱（TCGA）数据集下载201例CC患者的基因特异性DNA甲基化表达谱及相应临床信息，在肿瘤亚型分类后鉴定差异表达的基因特异性DNA甲基化。通过分析CC患者训练数据集的这些基因特异性DNA甲基化的表达数据，进一步构建风险评分模型。
共发现214种基因特异性DNA甲基化在CC不同亚型之间有显著表达，其中150种上调，64种下调。上调的基因特异性DNA甲基化占70.1%，下调的基因特异性DNA甲基化占29.9%。其中，获得了六种基因特异性DNA甲基化，包括甲基化波形蛋白和甲基化TFPI2，发现它们与CC患者的总生存状态显著相关。
利用这六种基因特异性DNA甲基化特征，将训练集中的患者分为低风险和高风险组。此外，基因特异性DNA甲基化靶基因与蛋白质磷酸化高度相关，这表明对靶基因编码蛋白磷酸化的进一步研究可能为CC的治疗提供新的视角。
