Yang Jie, Xu Qing-Chun, Wang Zhen-Yu, Lu Xun, Pan Liu-Kui, Wu Jun, Wang Chen
Department of Emergency Surgery, The Second People's Hospital of Wuhu, Wuhu, China.
J Comput Biol. 2021 Mar;28(3):330-344. doi: 10.1089/cmb.2019.0250. Epub 2020 Nov 4.
Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide. In this study, we aimed to explore the potential biomarkers and key regulatory pathways related to HCC using integrated bioinformatic analysis and validation. The microarray data of GSE12717 and GSE54238 were downloaded from the Gene Expression Omnibus database. A competing endogenous RNA (ceRNA) network was constructed based on potential long-noncoding RNA (lncRNA)-microRNA (miRNA)-mRNA interactions. A total of 191 mRNAs, 8 miRNAs, and 5 lncRNAs were selected to construct the ceRNA network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to predict their biological functions. The PI3K-Akt signaling pathway was significantly enriched. Kaplan-Meier survival analysis based on the Gene Expression Profiling Interactive Analysis (GEPIA) database was conducted for the weighted mRNAs and lncRNAs. The results showed that SRC, GMPS, CDK2, FEN1, EZH2, ZWINT, MTHFD1L, GINS2, and MAPKAPK5-AS1 were significantly upregulated in tumor tissues. The relative expression levels of these genes were significantly upregulated in HCC patients based on the StarBase database. For further validation, the expression levels of these genes were detected by real-time quantitative reverse transcription-polymerase chain reaction in 20 HCC tumor tissues and paired paracancerous tissues. Receiver operating characteristic analysis revealed that CDK2, MTHFD1L, SRC, ZWINT, and MAPKAPK5-AS1 had significant diagnostic value in HCC, but further studies are needed to explore their mechanisms in HCC.
肝细胞癌（HCC）是全球常见的恶性肿瘤。在本研究中，我们旨在通过综合生物信息学分析和验证来探索与HCC相关的潜在生物标志物和关键调控通路。从基因表达综合数据库下载了GSE12717和GSE54238的微阵列数据。基于潜在的长链非编码RNA（lncRNA）-微小RNA（miRNA）-信使RNA（mRNA）相互作用构建了竞争性内源性RNA（ceRNA）网络。共选择了191个mRNA、8个miRNA和5个lncRNA来构建ceRNA网络。使用基因本体论和京都基因与基因组百科全书（KEGG）通路分析来预测它们的生物学功能。PI3K-Akt信号通路显著富集。基于基因表达谱交互式分析（GEPIA）数据库对加权的mRNA和lncRNA进行了Kaplan-Meier生存分析。结果显示，SRC、GMPS、CDK2、FEN1、EZH2、ZWINT、MTHFD1L、GINS2和MAPKAPK5-AS1在肿瘤组织中显著上调。基于StarBase数据库，这些基因的相对表达水平在HCC患者中显著上调。为进一步验证，通过实时定量逆转录-聚合酶链反应检测了20对HCC肿瘤组织和癌旁组织中这些基因的表达水平。受试者工作特征分析显示，CDK2、MTHFD1L、SRC、ZWINT和MAPKAPK5-AS1在HCC中具有显著的诊断价值，但需要进一步研究来探索它们在HCC中的作用机制。
