三维 (3D) 染色质结构在癌症中经常发生改变。然而，其在肝细胞癌（HCC）发病过程中的变化仍然难以捉摸。应用Hi-C和RNA-seq研究HCC和ANHT的3D染色质景观和基因表达。 Hi-C Pro 用于生成全基因组原始相互作用矩阵，并通过迭代校正 (ICE) 进行标准化。此外，根据第一主成分（E1）将染色体分为不同的区室。此外，拓扑相关域 (TAD) 通过 WashU 表观基因组浏览器进行可视化。此外，使用 DESeq2 R 软件包进行 ANHT 和 HCC 的差异表达分析。此外，利用TCGA、qRT-PCR、免疫组织化学(IHC)等方法确认了与3D基因组结构改变相关的失调基因。结果：首先，chr1、chr2、chr5和chr11的染色体内相互作用显着不同，染色体间相互作用显着不同。 ANHT 和 HCC 之间的 chr4-chr10、chr13-chr21、chr15-chr22 和 chr16-chr19 存在显着差异，导致 HCC 中 TP53I3 和 ZNF738 上调，APOC3 和 APOA5 下调。其次，18 条染色体上的 49 个区室区域在 HCC 肿瘤发生过程中发生了显着转换（A-B 或 B-A），导致 RAP2A 上调。最后，在 HCC 组织中发现了位于 chr5: 6271000-6478000 上的肿瘤特异性 TAD 边界和增强子劫持，可能与 MED10 的表达升高有关，MED10 的表达与 HCC 患者的不良预后相关。这项研究证明了至关重要的作用HCC 肿瘤发生中的染色体结构变异和 HCC 潜在的新型生物标志物，为癌症精准医学的发展奠定了基础。© 2023。日本胃肠病学会。

Three-dimensional (3D) chromatin architecture frequently altered in cancer. However, its changes during the pathogenesis of hepatocellular carcinoma (HCC) remained elusive.Hi-C and RNA-seq were applied to study the 3D chromatin landscapes and gene expression of HCC and ANHT. Hi-C Pro was used to generate genome-wide raw interaction matrices, which were normalized via iterative correction (ICE). Moreover, the chromosomes were divided into different compartments according to the first principal component (E1). Furthermore, topologically associated domains (TADs) were visualized via WashU Epigenome Browser. Furthermore, differential expression analysis of ANHT and HCC was performed using the DESeq2 R package. Additionally, dysregulated genes associated with 3D genome architecture altered were confirmed using TCGA, qRT-PCR, immunohistochemistry (IHC), etc. RESULTS: First, the intrachromosomal interactions of chr1, chr2, chr5, and chr11 were significantly different, and the interchromosomal interactions of chr4-chr10, chr13-chr21, chr15-chr22, and chr16-chr19 are remarkably different between ANHT and HCC, which resulted in the up-regulation of TP53I3 and ZNF738 and the down-regulation of APOC3 and APOA5 in HCC. Second, 49 compartment regions on 18 chromosomes have significantly switched (A-B or B-A) during HCC tumorigenesis, contributing to up-regulation of RAP2A. Finally, a tumor-specific TAD boundary located on chr5: 6271000-6478000 and enhancer hijacking were identified in HCC tissues, potentially associated with the elevated expression of MED10, whose expression were associated with poor prognosis of HCC patients.This study demonstrates the crucial role of chromosomal structure variation in HCC oncogenesis and potential novel biomarkers of HCC, laying a foundation for cancer precision medicine development.© 2023. Japanese Society of Gastroenterology.