Chen Guolin, Zhang Wei, Ben Yiran
Department of Infectious Diseases, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Front Genet. 2021 Sep 9;12:741608. doi: 10.3389/fgene.2021.741608. eCollection 2021.
Hepatitis C virus (HCV) infection is a major cause of cirrhosis and hepatocellular carcinoma (HCC). Despite recent advances in the understanding of the biological basis of HCC development, the molecular mechanisms underlying HCV-induced HCC (HCC-HCV) remain unclear. The carcinogenic potential of HCV varies according to the genotype and mutation in its viral sequence. Moreover, regulatory pathways play important roles in many pathogenic processes. Therefore, identifying the pathways by which HCV induces HCC may enable improved HCC diagnosis and treatment. We employed a systematic approach to identify an important regulatory module in the process of HCV-HCC development to find the important regulators. First, an HCV-related HCC subnetwork was constructed based on the gene expression in HCC-HCV patients and HCC patients. A priority algorithm was then used to extract the module from the subnetworks, and all the regulatory relationships of the core genes of the network were extracted. Integrating the significantly highly mutated genes involved in the HCC-HCV patients, core regulatory modules and key regulators related to disease prognosis and progression were identified. The key regulatory genes including , , , and were found to play vital roles in HCV-HCC development. Based on the statistics analysis, , , and mutations are potential biomarkers for HCV-HCC prognosis at the genomic level, whereas has-miR-200c-5P is a potential biomarker for HCV-HCC prognosis at the expression level. We identified three significantly mutated genes and one differentially expressed miRNA, all related to HCC prognosis. As potential pathogenic factors of HCC, these genes and the miRNA could be new biomarkers for HCV-HCC diagnosis.
丙型肝炎病毒（HCV）感染是肝硬化和肝细胞癌（HCC）的主要病因。尽管最近在理解HCC发生的生物学基础方面取得了进展，但HCV诱导的HCC（HCC-HCV）的分子机制仍不清楚。HCV的致癌潜力因其病毒序列的基因型和突变而异。此外，调节途径在许多致病过程中起重要作用。因此，确定HCV诱导HCC的途径可能有助于改善HCC的诊断和治疗。我们采用系统方法来识别HCC-HCV发生过程中的一个重要调节模块，以找到重要的调节因子。首先，基于HCC-HCV患者和HCC患者的基因表达构建了一个HCV相关的HCC子网。然后使用优先级算法从子网中提取模块，并提取网络核心基因的所有调节关系。整合HCC-HCV患者中涉及的显著高度突变基因，确定了与疾病预后和进展相关的核心调节模块和关键调节因子。发现关键调节基因包括 、 、 和 在HCC-HCV发生中起重要作用。基于统计分析， 、 和 突变是基因组水平上HCC-HCV预后的潜在生物标志物，而has-miR-200c-5P是表达水平上HCC-HCV预后的潜在生物标志物。我们确定了三个显著突变基因和一个差异表达的miRNA，均与HCC预后相关。作为HCC的潜在致病因素，这些基因和miRNA可能是HCC-HCV诊断的新生物标志物。
