Department of Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
Department of Bioinformatics, Chongqing Medical University, Chongqing, China.
Biomed Res Int. 2021 Feb 23;2021:6662114. doi: 10.1155/2021/6662114. eCollection 2021.
Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and has poor outcomes. However, the potential molecular biological process underpinning the occurrence and development of HCC is still largely unknown. The purpose of this study was to identify the core genes related to HCC and explore their potential molecular events using bioinformatics methods. HCC-related expression profiles GSE25097 and GSE84005 were selected from the Gene Expression Omnibus (GEO) database, and the differentially expressed genes (DEGs) between 306 HCC tissues and 281 corresponding noncancerous tissues were identified using GEO2R online tools. The protein-protein interaction network (PPIN) was constructed and visualized using the STRING database. Gene Ontology (GO) and KEGG pathway enrichment analyses of the DEGs were carried out using DAVID 6.8 and KOBAS 3.0. Additionally, module analysis and centrality parameter analysis were performed by Cytoscape. The expression differences of key genes in normal hepatocyte cells and HCC cells were verified by quantitative real-time fluorescence polymerase chain reaction (qRT-PCR). Additionally, survival analysis of key genes was performed by GEPIA. Our results showed that a total of 291 DEGs were identified including 99 upregulated genes and 192 downregulated genes. Our results showed that the PPIN of HCC was made up of 287 nodes and 2527 edges. GO analysis showed that these genes were mainly enriched in the molecular function of protein binding. Additionally, KEGG pathway analysis also revealed that DEGs were mainly involved in the metabolic, cell cycle, and chemical carcinogenesis pathways. Interestingly, a significant module with high centrality features including 10 key genes was found. Among these, CDK1, NDC80, HMMR, CDKN3, and PTTG1, which were only upregulated in HCC patients, have attracted much attention. Furthermore, qRT-PCR also confirmed the upregulation of these five key genes in the normal human hepatocyte cell line (HL-7702) and HCC cell lines (SMMC-7721, MHCC-97L, and MHCC-97H); patients with upregulated expression of these five key genes had significantly poorer survival and prognosis. CDK1, NDC80, HMMR, CDKN3, and PTTG1 can be used as molecular markers for HCC. This finding provides potential strategies for clinical diagnosis, accurate treatment, and prognosis analysis of liver cancer.
肝细胞癌（HCC）是最常见的原发性肝癌，预后较差。然而，HCC 发生和发展的潜在分子生物学过程在很大程度上仍然未知。本研究旨在使用生物信息学方法鉴定与 HCC 相关的核心基因，并探讨其潜在的分子事件。从基因表达综合（GEO）数据库中选择了与 HCC 相关的表达谱 GSE25097 和 GSE84005，并用 GEO2R 在线工具鉴定了 306 例 HCC 组织和 281 例相应非癌组织之间的差异表达基因（DEGs）。使用 STRING 数据库构建和可视化蛋白质-蛋白质相互作用网络（PPIN）。使用 DAVID 6.8 和 KOBAS 3.0 对 DEGs 进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。此外，通过 Cytoscape 进行模块分析和中心性参数分析。通过定量实时荧光聚合酶链反应（qRT-PCR）验证正常肝细胞和 HCC 细胞中关键基因的表达差异。此外，通过 GEPIA 进行关键基因的生存分析。我们的结果表明，共鉴定出 291 个 DEGs，包括 99 个上调基因和 192 个下调基因。我们的结果表明，HCC 的 PPIN 由 287 个节点和 2527 个边组成。GO 分析表明，这些基因主要富集在蛋白质结合的分子功能上。此外，KEGG 通路分析还表明，DEGs 主要参与代谢、细胞周期和化学致癌途径。有趣的是，发现了一个具有高中心性特征的显著模块，其中包含 10 个关键基因。在这些基因中，CDK1、NDC80、HMMR、CDKN3 和 PTTG1 仅在 HCC 患者中上调，引起了广泛关注。此外，qRT-PCR 还证实了这 5 个关键基因在正常人类肝细胞系（HL-7702）和 HCC 细胞系（SMMC-7721、MHCC-97L 和 MHCC-97H）中的上调表达；这些关键基因上调表达的患者生存和预后明显较差。CDK1、NDC80、HMMR、CDKN3 和 PTTG1 可用作 HCC 的分子标志物。这一发现为肝癌的临床诊断、准确治疗和预后分析提供了潜在策略。
