The mRNA-miRNA-lncRNA Regulatory Network and Factors Associated with Prognosis Prediction of Hepatocellular Carcinoma

The aim of this study was to identify novel prognostic m RNA and micro RNA(mi RNA) biomarkers for hepatocellular carcinoma(HCC) using methods in systems biology. Differentially expressed m RNAs, mi RNAs, and long non-coding RNAs(lnc RNAs) were compared between HCC tumor tissues and normal liver tissues in The Cancer Genome Atlas(TCGA) database. Subsequently, a prognosis-associated m RNA co-expression network, an m RNA–mi RNA regulatory network, and an m RNA–mi RNA–lnc RNA regulatory network were constructed to identify prognostic biomarkers for HCC through Cox survival analysis. Seven prognosis-associated m RNA co-expression modules were obtained by analyzing these differentially expressed m RNAs. An expression module including 120 m RNAs was significantly correlated with HCC patient survival. Combined with patient survival data, several m RNAs and mi RNAs, including CHST4,SLC22 A8, 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-21-5 p indicated specific associations with several cancer-related pathways. The present study provides a bioinformatics method for biomarker screening, leading to the identification of an integrated m RNA–mi RNA–lnc RNA regulatory network and their co-expression patterns in relation to predicting HCC patient survival.