Genes of DLK1-DIO3 Locus and miR-379/656 Cluster is a Potential Diagnostic and Prognostic Marker in Patients with Hepatocellular Carcinoma: A Systems Biology Study

Abstract

BackgroundHepatocellular carcinoma is the sixth most common malignancy reported globally. This highlights the need for reliable biomarkers that can be employed for diagnostic and prognostic applications. The present study aimed to classify and characterize the clinical potential of DLK1-DIO3 and miR-379/656 cluster genes in hepatocellular carcinoma. MethodsWe extensively studied the clinical potential of DLK1-DIO3 genes through a comprehensive systems biology approach and assessed the diagnostic and prognostic potential of the genes associated with the region. Additionally, we have predicted the gene targets of the miR-379/656 cluster associated with the locus and have identified the gene ontology, pathway, and disease associations. ResultsWe report this region as a potential biomarker for hepatocellular carcinoma. About thirty clustered miRNAs, a long-non-coding RNA, and two coding genes of the region were underexpressed in tumors. ROC analysis identified 11 clustered miRNAs with diagnostic potential. Survival analyses identified MEG3 and the miR-379/656 cluster as prognostically significant. Further, the Random-Forest model predicted that the miRNA cluster classifies patients according to TNM staging. Furthermore, overrepresentation analysis identified several key pathways, molecular functions, and biological processes associated with the cluster gene targets. ConclusionOur study suggests that DLK1-DIO3 genes, miR-379/656 cluster, and its target gene network might be potential diagnostic and prognostic markers for HCC management and therapy.