Pils Dietmar, Steindl Elisabeth, Bachmayr-Heyda Anna, Dekan Sabine, Aust Stefanie
Division of General Surgery, Department of Surgery, Comprehensive Cancer Center (CCC) Vienna, Medical University of Vienna, 1090 Vienna, Austria.
Department of Obstetrics and Gynecology, Comprehensive Cancer Center (CCC) Vienna, Medical University of Vienna, 1090 Vienna, Austria.
Cancers (Basel). 2020 Aug 12;12(8):2257. doi: 10.3390/cancers12082257.
Epigenetics, CpG methylation of CpG islands (CGI) and gene bodies (GBs), plays an important role in gene regulation and cancer biology, the former established as a transcription regulator. Genome wide CpG methylation, summarized over GBs and CGIs, was analyzed for impact on overall survival (OS) in cancer. The averaged GB and CGI methylation status of each gene was categorized into methylated and unmethylated (defined) or undefined. Differentially methylated GBs and genes associated with their GB methylation status were compared to the corresponding CGI methylation states and biologically annotated. No relevant correlations of GB and CGI methylation or GB methylation and gene expression were observed. Summarized GB methylation showed impact on OS in ovarian, breast, colorectal, and pancreatic cancer, and glioblastoma, but not in lung cancer. In ovarian, breast, and colorectal cancer more defined GBs correlated with unfavorable OS, in pancreatic cancer with favorable OS and in glioblastoma more methylated GBs correlated with unfavorable OS. The GB methylation of genes were similar over different samples and even over cancer types; nevertheless, the clustering of different cancers was possible. Gene expression differences associated with summarized GB methylation were cancer specific. A genome-wide dysregulation of gene-body methylation showed impact on the outcome in different cancers.
表观遗传学，即CpG岛（CGI）和基因体（GB）的CpG甲基化，在基因调控和癌症生物学中起着重要作用，前者被确立为一种转录调节因子。分析了全基因组范围内总结于GB和CGI上的CpG甲基化对癌症患者总生存期（OS）的影响。将每个基因的平均GB和CGI甲基化状态分为甲基化和未甲基化（定义明确）或未定义。将差异甲基化的GB及其与GB甲基化状态相关的基因与相应的CGI甲基化状态进行比较，并进行生物学注释。未观察到GB和CGI甲基化或GB甲基化与基因表达之间的相关关系。总结的GB甲基化对卵巢癌、乳腺癌、结直肠癌、胰腺癌和胶质母细胞瘤的OS有影响，但对肺癌无影响。在卵巢癌、乳腺癌和结直肠癌中，更多定义明确的GB与不良OS相关，在胰腺癌中与良好OS相关，在胶质母细胞瘤中，更多甲基化的GB与不良OS相关。不同样本甚至不同癌症类型中基因的GB甲基化相似；然而，不同癌症的聚类是可能的。与总结的GB甲基化相关的基因表达差异具有癌症特异性。全基因组范围的基因体甲基化失调对不同癌症的预后有影响。
