Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, China.
Department of Hepatopancreatobiliary Surgery, Peking University Shenzhen Hospital, Shenzhen, China.
Pathol Oncol Res. 2021 Apr 2;27:601693. doi: 10.3389/pore.2021.601693. eCollection 2021.
Hepatocellular carcinoma (HCC) is a common cancer with poor prognosis. Due to the lack of effective biomarkers and its complex immune microenvironment, the effects of current HCC therapies are not ideal. In this study, we used the GSE57957 microarray data from Gene Expression Omnibus database to construct a co-expression network. The weighted gene co-expression network analysis and CIBERSORT algorithm, which quantifies cellular composition of immune cells, were used to identify modules related to immune cells. Four hub genes (EFTUD2, GAPDH, NOP56, PA2G4) were identified by co-expression network and protein-protein interactions network analysis. We examined these genes in TCGA database, and found that the four hub genes were highly expressed in tumor tissues in multiple HCC groups, and the expression levels were significantly correlated with patient survival time, pathological stage and tumor progression. On the other hand, methylation analysis showed that the up-regulation of EFTUD2, GAPDH, NOP56 might be due to the hypomethylation status of their promoters. Next, we investigated the correlations between the expression levels of four hub genes and tumor immune infiltration using Tumor Immune Estimation Resource (TIMER). Gene set variation analysis suggested that the four hub genes were associated with numerous pathways that affect tumor progression or immune microenvironment. Overall, our results showed that the four hub genes were closely related to tumor prognosis, and may serve as targets for treatment and diagnosis of HCC. In addition, the associations between these genes and immune infiltration enhanced our understanding of tumor immune environment and provided new directions for the development of drugs and the monitoring of tumor immune status.
肝细胞癌 (HCC) 是一种预后较差的常见癌症。由于缺乏有效的生物标志物和其复杂的免疫微环境，目前 HCC 治疗的效果并不理想。在本研究中，我们使用来自基因表达综合数据库的 GSE57957 微阵列数据构建了一个共表达网络。加权基因共表达网络分析和 CIBERSORT 算法（用于量化免疫细胞的细胞组成）用于识别与免疫细胞相关的模块。通过共表达网络和蛋白质-蛋白质相互作用网络分析，鉴定出四个枢纽基因（EFTUD2、GAPDH、NOP56、PA2G4）。我们在 TCGA 数据库中检查了这些基因，发现这四个枢纽基因在多个 HCC 组的肿瘤组织中高表达，并且表达水平与患者的生存时间、病理分期和肿瘤进展显著相关。另一方面，甲基化分析表明，EFTUD2、GAPDH、NOP56 的上调可能是由于其启动子的低甲基化状态。接下来，我们使用肿瘤免疫估计资源 (TIMER) 研究了四个枢纽基因的表达水平与肿瘤免疫浸润之间的相关性。基因集变异分析表明，这四个枢纽基因与影响肿瘤进展或免疫微环境的众多途径有关。总体而言，我们的研究结果表明，这四个枢纽基因与肿瘤预后密切相关，可能作为 HCC 治疗和诊断的靶点。此外，这些基因与免疫浸润之间的关联增强了我们对肿瘤免疫环境的理解，为药物开发和肿瘤免疫状态监测提供了新的方向。
