Integrative analysis of tissue and circulating miRNAs as biomarkers for progression and survival in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with limited biomarkers available for early diagnosis and risk stratification. In this study, we performed an integrative analysis of tissue and circulating microRNA (miRNA) expression profiles to identify candidates linked to disease progression and clinical outcomes. Tumor miRNA data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) and serum miRNA data from the Gene Expression Omnibus (GSE113740) were analyzed using differential expression, survival analysis, functional enrichment, and clinical subgroup evaluation. We identified 16 significantly dysregulated miRNAs in HCC tissues, including hsa-miR-187 and hsa-miR-6718, which were associated with poor survival, and hsa-miR-5589, which showed a protective effect. Clinical analyses revealed stage-specific upregulation of hsa-miR-106b and downregulation of the hsa-miR-124 family in metastatic tumors. Functional enrichment highlighted pathways such as PI3K-Akt, MAPK signalling, and nucleocytoplasmic transport. Circulating miRNAs, including hsa-miR-3619-3p, hsa-miR-1290, and hsa-miR-1185-2-3p, correlated with AFP levels and disease stage, underscoring their value as non-invasive biomarkers. These findings demonstrate that integrated analysis of tissue and serum miRNAs can identify clinically relevant biomarkers and potential therapeutic targets in HCC.