Alterations in DNA methylation patterns are considered early events in hepatocellular carcinoma (HCC). However, their mechanism and significance remain to be elucidated. We studied the genome-wide DNA methylation landscape of HCC by applying whole-genome bisulfite sequencing (WGBS) techonlogy. Overall, HCC exhibits a genome-wide hypomethylation pattern. After further annotation, we obtained 590 differentially hypermethylated genes (hyper-DMGs) and 977 differentially hypomethylated genes (hypo-DMGs) from three groups. Hyper-DMGs were mainly involved in ascorbate and alternate metabolism pathways, while hypo-DMGs were mainly involved in focal adhesion. By integrating the DMGs with HCC-related differentially expressed genes (DEGs) and DMGs from the TCGA database, we constructed prognostic model based on thirteen aberrantly methylated DEGs, and verified our prognostic model in GSE14520 dataset. This study compares the patterns of global epigenomic DNA methylation during the development of HCC, focusing on the role of DNA methylation in the early occurrence and development of HCC, providing a direction for future research on its epigenetic mechanism.

DNA甲基化模式的改变被认为是肝细胞癌（HCC）的早期事件。然而，它们的作用机制和意义仍有待阐明。我们通过应用全基因组亚硫酸氢盐测序 (WGBS) 技术研究了 HCC 的全基因组 DNA 甲基化景观。总体而言，HCC 表现出全基因组低甲基化模式。经过进一步注释，我们从三组中获得了 590 个差异性高甲基化基因（hypo-DMGs）和 977 个差异性低甲基化基因（hypo-DMGs）。Hyper-DMGs主要参与抗坏血酸和替代代谢途径，而hypo-DMGs主要参与粘着斑。通过将 DMG 与 TCGA 数据库中的 HCC 相关差异表达基因 (DEG) 和 DMG 整合，我们构建了基于 13 个异常甲基化 DEG 的预后模型，并在 GSE14520 数据集中验证了我们的预后模型。本研究比较了HCC发展过程中全球表观基因组DNA甲基化的模式，重点探讨了DNA甲基化在HCC早期发生和发展中的作用，为其表观遗传机制的未来研究提供了方向。