miRNA-mRNA Regulatory Network and Factors Associated with Prediction of Prognosis in Hepatocellular Carcinoma.

Abstract

The aim of this study was to identify novel gene and miRNA biomarkers of risk and prognostic factors for hepatocarcinogenesis using methods in systems biology. Differentially expressed genes (DEGs), microRNAs (miRNAs), and long non-coding RNA (lncRNAs) were compared between hepatocellular carcinoma (HCC) tumour tissue and normal liver tissues in the Cancer Genome Atlas (TCGA) database. Subsequently, the prognosis-associated gene co-expression network, mRNA-miRNA, and mRNA-miRNA-lncRNA regulatory networks were constructed to identify biomarkers of risk for HCC through Cox survival analysis. Seven prognosis-associated gene co-expression modules were obtained by analyzing these DEGs. An expression module including 120 genes significantly correlated with HCC patient survival. Combined with patient survival data, several mRNAs and miRNAs, including CHST4, SLC22A8, STC2, hsa-miR-326, and hsa-miR-21 were identified from the network to predict HCC patient prognosis. Clinical significance was investigated using tissue microarray analysis of samples from 258 patients with HCC. Functional annotation of hsa-miR-326 and hsa-miR-21-5p indicated specific associations with several cancer-related pathways. The present study provides a bioinformatics method for biomarker screening, which led to the identification of an integrated mRNA-miRNA-lncRNA regulatory network and their co-expression in relation to predicting HCC patient survival.