Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province 150086, China.
Department of Graduation, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province 150086, China.
Gene. 2025 Jan 15;933:148937. doi: 10.1016/j.gene.2024.148937. Epub 2024 Sep 11.
Hepatocellular carcinoma (HCC), theseventh most common cancer worldwide, is characterized by a high mortality rate, advanced diagnosis, and susceptibility to extrahepatic metastasis. Numerous studies have shown that DNA methylation is a crucial factor in epigenetic modifications and regulation of carcinogenesis.
HCC patient data were sourced from the TCGA dataset as a training set, while GSE116174 was used as an external validation set for verification. Differential methylation and expression analyses were performed on HCC samples with and without extrahepatic metastasis. In the intersecting genes, the relationship between methylation and expression levels of the intersecting genes was analyzed. Genes with a correlation coefficient≥|0.30| and P<0.05 were identified as methylation driver genes. Cox regression analysis was conducted to identify genes associated with HCC prognosis and establish a risk score. Subsequently, a prognostic model was established and validated using Cox regression analysis incorporating the risk score and other clinical factors. Using immunohistochemistry to evaluate the expression of DHX58 and EIF5A2 in HCC tissues with and without extrahepatic metastasis. Immunoinfiltration analysis was performed on the HCC samples using CIBERSORT.
Our research identified eight methylation driver genes for HCC extrahepatic metastasis, of which two genes (DHX58 and EIF5A2) were associated with HCC patient prognosis. And the study further constructed and validated the risk score and prognostic model. Immunoinfiltration analysis showed that M0 macrophage abundance was correlated with the prognosis of HCC patients. Immunohistochemistry revealed differences in DHX58 and EIF5A2 expression between HCC tissues with and without extrahepatic metastasis, consistent with our bioinformatics findings.
肝细胞癌（HCC）是全球第七大常见癌症，其死亡率高，诊断较晚，易发生肝外转移。大量研究表明，DNA 甲基化是表观遗传修饰和肿瘤发生调控的重要因素。
从 TCGA 数据集获取 HCC 患者数据作为训练集，使用 GSE116174 作为外部验证集进行验证。对有/无肝外转移的 HCC 样本进行差异甲基化和表达分析。在交集基因中，分析交集基因的甲基化和表达水平之间的关系。鉴定出相关系数≥|0.30|且 P<0.05 的基因作为甲基化驱动基因。采用 Cox 回归分析鉴定与 HCC 预后相关的基因，并建立风险评分。然后，使用 Cox 回归分析纳入风险评分和其他临床因素，建立并验证预后模型。使用免疫组织化学评估有/无肝外转移的 HCC 组织中 DHX58 和 EIF5A2 的表达。使用 CIBERSORT 对 HCC 样本进行免疫浸润分析。
本研究确定了 8 个与 HCC 肝外转移相关的甲基化驱动基因，其中 2 个基因（DHX58 和 EIF5A2）与 HCC 患者的预后相关。并进一步构建和验证了风险评分和预后模型。免疫浸润分析表明，M0 巨噬细胞丰度与 HCC 患者的预后相关。免疫组织化学显示，DHX58 和 EIF5A2 在有/无肝外转移的 HCC 组织中的表达存在差异，与我们的生物信息学发现一致。
