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

Background: Hepatocellular 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 delta like non-canonical Notch ligand 1-type III iodothyronine deiodinase (DLK1-DIO3) and miR-379/656 cluster genes in hepatocellular carcinoma.

Methods: We 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.

Results: We 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. The receiver operating characteristic analysis identified 11 clustered miRNAs with diagnostic potential. Survival analyses identified maternally expressed gene 3 and the miR-379/656 cluster as prognostically significant. Further, the random forest model predicted that the miRNA cluster classifies patients according to Tumor, Node, Metastasis (TNM) staging. Furthermore, overrepresentation analysis identified several key pathways, molecular functions, and biological processes associated with the cluster gene targets.

Conclusion: Our study suggests that DLK1-DIO3 genes, miR-379/656 cluster, and its target gene network might be potential diagnostic and prognostic markers for hepatocellular carcinoma management and therapy.

Keywords: DLK1-DIO3; diagnosis; hepatocellular carcinoma; miR-379/656 cluster; overall survival.