Yang X, Li Y, Wu D, Ma Y, Zhou S
National Center for International Research of Bio-targeting Theranostics//Guangxi Key Laboratory of Bio-targeting Theranostics//Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy//Guangxi Talent Highland of Bio-targeting Theranostics, Nanning 530021, China.
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Guangxi Medical University, Nanning 530021, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2022 Jun 20;42(6):815-823. doi: 10.12122/j.issn.1673-4254.2022.06.04.
To explore the marker genes correlated with the prognosis, progression and clinical diagnosis of hepatocellular carcinoma (HCC) based on bioinformatics methods.
The TCGA-LIHC, GSE84432, GSE143233 and GSE63898 datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed. The differentially expressed genes (DEGs) shared by different disease types were obtained using GEO2R and edge R packages, and Gene Ontology (GO) and Kyoto Gene and Genome Encyclopedia (KEGG) enrichment analyses of the DEGs were performed. The expression levels of these DEGs in normal and cancerous tissues were verified in TCGA-LIHC to identify the upregulated genes in HCC. Survival analysis, receiver-operating characteristic (ROC) curve analysis, and correlation analysis between the key genes and the clinical features of the patients were carried out using the R language. The differential expressions of 15 key genes were verified in clinical samples of HCC and adjacent tissues using RT-qPCR.
A total of 118 common DEGs were obtained in the database, and among them two genes, namely ATPase Na +/K + transport subunit beta 3 (ATP1B3) and actin regulator (ENAH), showed increased expressions with disease progression. Survival analysis combined with the TCGA-LIHC dataset suggested that high expressions of ATP1B3 and ENAH were both significantly correlated with a poor prognosis of HCC patients ( < 0.05), and their AUC values were 0.821 and 0.933, respectively. A high expression of ATP1B3 was correlated with T stage, pathological stage and pathological grade of the tumors ( < 0.05), while that of ENAH was associated only with an advanced tumor grade ( < 0.05). The results of RT-qPCR showed that ATP1B3 and ENAH were both significantly upregulated in clinical HCC tissues ( < 0.05).
ATPIB3 and ENAH are both upregulated in HCC, and their high expressions may serve as biomarkers of progression of liver diseases and a poor prognosis of HCC.
基于生物信息学方法探索与肝细胞癌（HCC）预后、进展及临床诊断相关的标志物基因。
分析来自癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）的TCGA-LIHC、GSE84432、GSE143233和GSE63898数据集。使用GEO2R和edgeR软件包获得不同疾病类型共有的差异表达基因（DEG），并对DEG进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析。在TCGA-LIHC中验证这些DEG在正常组织和癌组织中的表达水平，以确定HCC中的上调基因。使用R语言进行生存分析、受试者工作特征（ROC）曲线分析以及关键基因与患者临床特征之间的相关性分析。使用RT-qPCR在HCC临床样本和癌旁组织中验证15个关键基因的差异表达。
在数据库中总共获得118个常见DEG，并发现其中两个基因，即ATP酶Na+/K+转运亚基β3（ATP1B3）和肌动蛋白调节因子（ENAH），其表达随疾病进展而增加。结合TCGA-LIHC数据集的生存分析表明，ATP1B3和ENAH的高表达均与HCC患者的不良预后显著相关（<0.05），其AUC值分别为0.8
