Unveiling miRNA–Gene\nRegulatory Axes as Promising\nBiomarkers for Liver Cirrhosis and Hepatocellular Carcinoma

Liver cirrhosis, a severe scarring condition of the liver\nwith\nthe potential to progress to hepatocellular carcinoma (HCC), necessitates\nthe development of reliable biomarkers for early detection due to\nthe asymptomatic nature of its early stages. Recent discoveries in\nmicroRNAs (miRNAs) hold promise for a noninvasive test, with the potential\nto significantly improve patient outcomes. Building upon these promising\nfindings, this study investigates gene expression data, identifying\ndistinct sets of DEGs and DEMs using GEO2R. Subsequently, a gene–miRNA\nnetwork was constructed using Cytoscape to explore potential interactions\nbetween DEMs and their target genes (DEGs). Boxplot analysis was carried\nout to identify and validate differences in gene expression between\nhealthy and diseased tissues. This analysis revealed four significantly\ndifferentially expressed genes: CAV1, PEA15, EMP1, and ENAH. Notably,\nsubsequent survival analysis demonstrated that EMP1 and ENAH significantly\nimpact overall patient survival. Intriguingly, the constructed network\nidentified several potential regulatory axes: hsa-miR-191-5p/ENAH,\nhsa-miR-3158-3p/ENAH, hsa-miR-371a-5p/ENAH, and hsa-miR-6753-5p/EMP1.\nCrucially, a direct comparison of DEGs and DEMs between liver cirrhosis\nand HCC pinpointed AGO3, NCOA3, and TNPO1, along with their regulatory\nelements, as potential key drivers of HCC development in cirrhotic\npatients, underscoring their importance as targets for early diagnostic\nand therapeutic strategies. Finally, immunohistochemical (IHC) analysis\nnot only validates our findings but also reiterates the novelty of\nthe identified genes. Overall, elucidating the role of these novel\ngenes and regulatory elements could pave the way for an earlier and\nmore accurate diagnosis of liver diseases.