Unveiling miRNA–Gene Regulatory Axes as Promising Biomarkers for Liver Cirrhosis and Hepatocellular Carcinoma

Abstract

Liver cirrhosis, a severe scarring condition of the liver with the potential to progress to hepatocellular carcinoma (HCC), necessitates the development of reliable biomarkers for early detection due to the asymptomatic nature of its early stages. Recent discoveries in microRNAs (miRNAs) hold promise for a noninvasive test, with the potential to significantly improve patient outcomes. Building upon these promising findings, this study investigates gene expression data, identifying distinct sets of DEGs and DEMs using GEO2R. Subsequently, a gene–miRNA network was constructed using Cytoscape to explore potential interactions between DEMs and their target genes (DEGs). Boxplot analysis was carried out to identify and validate differences in gene expression between healthy and diseased tissues. This analysis revealed four significantly differentially expressed genes: CAV1, PEA15, EMP1, and ENAH. Notably, subsequent survival analysis demonstrated that EMP1 and ENAH significantly impact overall patient survival. Intriguingly, the constructed network identified several potential regulatory axes: hsa-miR-191-5p/ENAH, hsa-miR-3158-3p/ENAH, hsa-miR-371a-5p/ENAH, and hsa-miR-6753-5p/EMP1. Crucially, a direct comparison of DEGs and DEMs between liver cirrhosis and HCC pinpointed AGO3, NCOA3, and TNPO1, along with their regulatory elements, as potential key drivers of HCC development in cirrhotic patients, underscoring their importance as targets for early diagnostic and therapeutic strategies. Finally, immunohistochemical (IHC) analysis not only validates our findings but also reiterates the novelty of the identified genes. Overall, elucidating the role of these novel genes and regulatory elements could pave the way for an earlier and more accurate diagnosis of liver diseases.