Development and validation of an exosomal microRNA prognostic signature for BCLC stage A/B hepatocellular carcinoma

Hepatocellular carcinoma (HCC) exhibits remarkable prognostic heterogeneity within identical Barcelona Clinic Liver Cancer (BCLC) stages, thus requiring more precise molecular biomarkers. Exosomal microRNAs (miRNAs) are stable, non-invasive biomarkers that faithfully reflect the molecular characteristics of parental tumor cells. This study aimed to develop and validate an exosomal miRNA prognostic signature specifically for BCLC stage A/B HCC patients. Small RNA sequencing was performed on plasma exosomes from 80 HCC patients and 80 healthy controls. Five significantly upregulated miRNAs (miR-21-5p, miR-122-5p, miR-192-5p, miR-223-3p, miR-483-5p) were identified to construct a prognostic model by Cox regression, which was validated in an internal validation cohort. The signature effectively stratified patients into high and low risk groups with significantly different overall survival (OS, P < 0.05). Time-dependent receiver operating characteristic (ROC) analysis showed area under the curve (AUC) of 0.814, 0.796, and 0.788 for 1-, 3-, and 5-year OS, respectively. High-risk patients were associated with larger tumor size, more lesions, and higher prevalence of vascular invasion. Collectively, this signature serves as a promising non-invasive prognostic biomarker to facilitate personalized risk assessment and treatment decision-making for BCLC stage A/B HCC patients.