title: Identification of key genes in hepatocellular carcinoma and validation of the candidate gene, cdc25a, using gene set enrichment analysis, meta-analysis and cross-species comparison.
abstract: The aim of the present study was to determine key pathways and genes involved in the pathogenesis of hepatocellular carcinoma (HCC) through bioinformatic analyses of HCC microarray data based on cross-species comparison. Microarray data of gene expression in HCC in different species were analyzed using gene set enrichment analysis (GSEA) and meta-analysis. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to determine the mRNA and protein expression levels of cdc25a, one of the identified candidate genes, in human, rat and tree shrew samples. The cell cycle pathway had the largest overlap between the GSEA and meta-analysis. Meta-analyses showed that 25 genes, including cdc25a, in the cell cycle pathway were differentially expressed. Cdc25a mRNA levels in HCC tissues were higher than those in normal liver tissues in humans, rats and tree shrews, and the expression level of cdc25a in HCC tissues was higher than in corresponding paraneoplastic tissues in humans and rats. In human HCC tissues, the cdc25a mRNA level was significantly correlated with clinical stage, portal vein tumor thrombosis and extrahepatic metastasis. Western blotting showed that, cdc25a protein levels were significantly upregulated in HCC tissues in humans, rats and tree shrews. In conclusion, GSEA and meta-analysis can be combined to identify key molecules and pathways involved in HCC. This study demonstrated that the cell cycle pathway and the cdc25a gene may be crucial in the pathogenesis and progression of HCC.
authors.affiliation: Department of Research, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Research, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Research, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Research, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Lingqun
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Research, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Research, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Ou
authors.affiliation: Department of Research, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Chun
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Research, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Jianjia
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Research, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Chengpiao
authors.initials: C
authors.lastname: Luo
authors.affiliation: The Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi 530022, P.R. China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Research, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Ji
authors.initials: J
authors.lastname: Cao
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015203:Reproducibility of Results; D012788:Shrews; D013045:Species Specificity; D020687:cdc25 Phosphatases / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases