Integrative analysis of DNA methylation and microRNA expression reveals mechanisms of disparity in hepatocellular carcinoma [RNA-Seq]

We evaluate the epigenetic mechanisms of racial disparity in HCC through an integrated analysis of DNA methylation, miRNA, and combined regulation of gene expression. Specifically, we acquired DNA methylation, mRNA-seq, and miRNA-seq data through the analysis of tumor and adjacent normal liver tissues from African Americans (AA) and European Americans (EA) with HCC. Results: Using mixed ANOVA, we identified cytosine-phosphate-guanine (CpG) sites, mRNAs, and miRNAs that are statistically significantly altered in HCC vs. adjacent normal in a race-specific manner. Through integrative analysis, we identified significantly differentially expressed genes in HCC with disparate epigenetic regulation, associated with changes in miRNA expression for AA and DNA methylation for EA. Overall design: mRNA profiles of 16 HCC and 16 adjacent normal liver tissue本研究通过整合分析DNA甲基化（DNA methylation）、微小RNA（miRNA）以及基因表达联合调控模式，探究肝细胞癌（Hepatocellular Carcinoma, HCC）种族差异的表观遗传机制。 具体而言，本研究收集了肝细胞癌患者的肿瘤组织与配对癌旁正常肝组织的测序数据，涵盖非裔美国人（African Americans, AA）与欧裔美国人（European Americans, EA）队列的DNA甲基化测序、mRNA测序（mRNA-seq）以及微小RNA测序（miRNA-seq）数据。 结果：本研究采用混合方差分析（mixed ANOVA），筛选出在肝细胞癌与癌旁正常组织间呈现种族特异性显著差异的胞嘧啶-磷酸-鸟嘌呤（CpG）位点、信使RNA（mRNA）以及微小RNA（miRNA）。通过整合分析，本研究进一步鉴定出表观遗传调控模式存在显著差异的肝细胞癌差异表达基因，其中非裔美国人队列的差异表达基因与微小RNA表达变化相关，欧裔美国人队列则与DNA甲基化改变相关。 整体实验设计：包含16例肝细胞癌组织与16例配对癌旁正常肝组织的mRNA表达谱。