Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Gene. 2019 May 25;698:9-18. doi: 10.1016/j.gene.2019.02.062. Epub 2019 Feb 27.
Hepatocellular carcinoma (HCC) is one type of the most common malignancies. However, the underlying molecular mechanisms involved in the development of HCC remain unknown. To identify the candidate genes in the progression of HCC, gene expression profiles GSE14520, GSE54236, GSE57957 and GSE64041 were downloaded from the Gene Expression Omnibus database (GEO). A total of 405 tumor and 399 para-carcinoma samples from patients with HCC were examined to identify the differentially expressed genes (DEGs), followed by function enrichment analyses including Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. A total of 78 DEGs were screened, including 62 downregulated genes and 16 upregulated genes. Subsequently, the protein-protein interaction network (PPI) was constructed using the Search Tool for Retrieval of Interacting Genes (STRING) database. The module analysis and Hub genes validation were performed using Cytoscape software. Hierarchical clustering of hub genes was evaluated using UCSC Cancer Genomics Browser. Survival analyses of Hub genes were performed using Kaplan Meier Plotter database. Genes specifically expressed in the liver were analyzed using GENEVESTIGATOR database. CYP2C8 was identified as one of the most promising molecules among all the candidate genes. The expression profile of CYP2C8 in HCC was analyzed using ONCOMINE and UALCAN database. The expression levels of CYP2C8 in HCC samples and hepatoma cells were verified using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry analysis. In summary, DEGs and hub genes were identified in the present study, which provides novel insight on the development of HCC. CYP2C8 was downregulated in HCC and could be a potential prognostic biomarker.
肝细胞癌（HCC）是最常见的恶性肿瘤之一。然而，HCC 发生发展的确切分子机制尚不清楚。为了鉴定 HCC 进展过程中的候选基因，从基因表达综合数据库（GEO）中下载基因表达谱 GSE14520、GSE54236、GSE57957 和 GSE64041。共检测了来自 HCC 患者的 405 个肿瘤和 399 个癌旁样本，以鉴定差异表达基因（DEGs），随后进行功能富集分析，包括基因本体论（GO）功能和京都基因与基因组百科全书（KEGG）通路。筛选出 78 个 DEGs，包括 62 个下调基因和 16 个上调基因。随后，使用 Search Tool for Retrieval of Interacting Genes（STRING）数据库构建蛋白质-蛋白质相互作用网络（PPI）。使用 Cytoscape 软件进行模块分析和 Hub 基因验证。使用 UCSC Cancer Genomics Browser 评估 Hub 基因的层次聚类。使用 Kaplan Meier Plotter 数据库对 Hub 基因进行生存分析。使用 GENEVESTIGATOR 数据库分析肝脏特异性表达的基因。CYP2C8 被确定为所有候选基因中最有前途的分子之一。使用 ONCOMINE 和 UALCAN 数据库分析 CYP2C8 在 HCC 中的表达谱。使用逆转录-定量聚合酶链反应（RT-qPCR）和免疫组织化学分析验证 CYP2C8 在 HCC 样本和肝癌细胞中的表达水平。总之，本研究鉴定了差异表达基因和 Hub 基因，为 HCC 的发生发展提供了新的见解。CYP2C8 在 HCC 中下调，可能是一个潜在的预后生物标志物。
