Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
State Key Laboratory of Modern Optical Instrumentations, Centre for Optical and Electromagnetic Research, College of Optical Science and Engineering, International Research Center for Advanced Photonics, Zhejiang University, Hangzhou, China.
DNA Cell Biol. 2023 Mar;42(3):140-150. doi: 10.1089/dna.2022.0384.
Hepatocellular carcinoma (HCC), a common primary liver cancer, is the third leading cause of death worldwide. DNA methylation changes are common in HCC and have been studied to be associated with hepatocarcinogenesis. In our study, we used the MassARRAY EpiTYPER technology to investigate the methylation differences of deleted in liver cancer 1 () (isoform 1 and 3) promoter between HCC tissues and corresponding adjacent noncancerous tissues and the association between methylation levels and clinicopathological features. In addition, the modified CRISPR-Cas9 system and the DNA methyltransferase inhibitor (DNMTi) were utilized to explore the functional correlation of epigenetic modifications and gene regulation. The methylation levels of the isoforms in HCC samples were found significantly lower than those in the adjacent noncancerous tissues (all < 0.0001). Also, we found that the expression of could be bidirectionally regulated by the modified CRISPR-Cas9 system and the DNMTi. Moreover, the hypomethylation of in HCC samples was connected with the presence of satellite lesions ( = 0.0305) and incomplete tumor capsule ( = 0.0204). Receiver operator characteristic curve analysis demonstrated that the methylation levels of could be applied to discriminate HCC patients (area under the curve = 0.728, < 0.0001). The hypomethylation status was a key regulatory mechanism of expression and might serve as a potential biomarker for HCC.
肝细胞癌（HCC）是一种常见的原发性肝癌，是全球第三大致死原因。DNA 甲基化改变在 HCC 中很常见，并且已经研究发现与肝癌发生有关。在我们的研究中，我们使用 MassARRAY EpiTYPER 技术研究 HCC 组织和相应的相邻非癌组织中缺失肝癌 1（）（异构体 1 和 3）启动子的甲基化差异，以及甲基化水平与临床病理特征的关联。此外，还利用改良的 CRISPR-Cas9 系统和 DNA 甲基转移酶抑制剂（DNMTi）来探讨表观遗传修饰和基因调控的功能相关性。我们发现 HCC 样本中 异构体的甲基化水平明显低于相邻非癌组织（均 < 0.0001）。此外，我们发现修饰后的 CRISPR-Cas9 系统和 DNMTi 可以双向调节 的表达。此外，HCC 样本中 的低甲基化与卫星病变的存在（ = 0.0305）和不完全肿瘤包膜（ = 0.0204）有关。受试者工作特征曲线分析表明， 甲基化水平可用于区分 HCC 患者（曲线下面积 = 0.728， < 0.0001）。低甲基化状态是 表达的关键调节机制，可能作为 HCC 的潜在生物标志物。
