Wang Yao, Liu Dandan, Jin Xin, Song Hongwei, Lou Ge
Department of Gynecology, The Affiliated Tumor Hospital, Harbin Medical University, 150081 Harbin, China; Department of Gynaecology and Obstetrics, The General Hospital of Daqing Oil Field, 163000 Daqing, China.
Department of Gynaecology and Obstetrics, The General Hospital of Daqing Oil Field, 163000 Daqing, China.
Pathol Res Pract. 2019 Jan;215(1):137-143. doi: 10.1016/j.prp.2018.11.002. Epub 2018 Nov 11.
Aberrant DNA methylation has been implicated in the development of the majority of human cancers. However, the association of aberrant DNA methylation with the clinical characteristics of uterine corpus endometrial carcinoma (UCEC) has not been fully explored. We performed an integrative analysis in order to examine the genome-wide DNA methylation profile and the gene expression profile of 432 UCEC samples and 46 normal tissue samples. A total of 793 differentially methylated regions (DMRs) that were associated with 472 protein-coding genes were identified, including 622 hypermethylated DMRs and 171 hypomethylated DMRs. These DMRs were capable of differentiating UCEC from normal tissues with an accuracy of 99.07% using an unsupervised hierarchical clustering method. The genomic analysis suggested that the hypermethylated DMRs were located in CpG island regions nearer to the transcription start site (TSS) compared with the hypomethylated DMRs. Functional analysis for genes associated with DMRs revealed an enrichment of methylated genes that were involved in key cancer-related biological processes and pathways, such as cell adhesion, cell differentiation and the cAMP signaling pathway. Finally, we performed a correlation analysis of the methylation levels of DMRs and patient survival time, and identified 130 DMRs. These molecular markers could classify patients into high-risk and low-risk groups with significantly different overall survival. Taken together, the present study revealed the potential applications of the detection of aberrant DNA methylation as a valuable prognostic marker for UCEC. The current findings may aid the therapeutic exploitation of UCEC treatment strategies and improve our understanding regarding the regulation of methylation in UCEC.
异常的DNA甲基化与大多数人类癌症的发生有关。然而，异常DNA甲基化与子宫体子宫内膜癌（UCEC）临床特征之间的关联尚未得到充分研究。我们进行了一项综合分析，以检查432例UCEC样本和46例正常组织样本的全基因组DNA甲基化谱和基因表达谱。共鉴定出793个与472个蛋白质编码基因相关的差异甲基化区域（DMR），包括622个高甲基化DMR和171个低甲基化DMR。使用无监督层次聚类方法，这些DMR能够以99.07%的准确率区分UCEC和正常组织。基因组分析表明，与低甲基化DMR相比，高甲基化DMR位于更靠近转录起始位点（TSS）的CpG岛区域。对与DMR相关基因的功能分析揭示了甲基化基因在关键癌症相关生物学过程和途径中的富集，如细胞粘附、细胞分化和cAMP信号通路。最后，我们对DMR的甲基化水平与患者生存时间进行了相关性分析，确定了130个DMR。这些分子标志物可将患者分为总生存期显著不同的高风险组和低风险组。综上所述，本研究揭示了检测异常DNA甲基化作为UCEC有价值的预后标志物的潜在应用。目前的研究结果可能有助于UCEC治疗策略的治疗性开发，并增进我们对UCEC中甲基化调控的理解。
