Transcriptome analysis revealed key prognostic genes and microRNAs in hepatocellular carcinoma.

BACKGROUND

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. However, the molecular mechanisms involved in HCC remain unclear and are in urgent need of elucidation. Therefore, we sought to identify biomarkers in the prognosis of HCC through an integrated bioinformatics analysis.

METHODS

Messenger RNA (mRNA) expression profiles were obtained from the Gene Expression Omnibus database and The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) for the screening of common differentially expressed genes (DEGs). Function and pathway enrichment analysis, protein-protein interaction network construction and key gene identification were performed. The significance of key genes in HCC was validated by overall survival analysis and immunohistochemistry. Meanwhile, based on TCGA data, prognostic microRNAs (miRNAs) were decoded using univariable and multivariable Cox regression analysis, and their target genes were predicted by miRWalk.

RESULTS

Eleven hub genes (upregulated ASPM, AURKA, CCNB2, CDC20, PRC1 and TOP2A and downregulated AOX1, CAT, CYP2E1, CYP3A4 and HP) with the most interactions were considered as potential biomarkers in HCC and confirmed by overall survival analysis. Moreover, AURKA, PRC1, TOP2A, AOX1, CYP2E1, and CYP3A4 were considered candidate liver-biopsy markers for high risk of developing HCC and poor prognosis in HCC. Upregulation of hsa-mir-1269b, hsa-mir-518d, hsa-mir-548aq, hsa-mir-548f-1, and hsa-mir-6728, and downregulation of hsa-mir-139 and hsa-mir-4800 were determined to be risk factors of poor prognosis, and most of these miRNAs have strong potential to help regulate the expression of key genes.

CONCLUSIONS

This study undertook the first large-scale integrated bioinformatics analysis of the data from Illumina BeadArray platforms and the TCGA database. With a comprehensive analysis of transcriptional alterations, including mRNAs and miRNAs, in HCC, our study presented candidate biomarkers for the surveillance and prognosis of the disease, and also identified novel therapeutic targets at the molecular and pathway levels.