Integrative Analysis of Exosomal MIR-122-5p and Gut Microbiota in Predicting Prognosis and Sorafenib Response in Hepatocellular Carcinoma

Abstract

Hepatocellular Carcinoma (HCC) is a leading cause of cancer-related death, with limited predictive biomarkers for prognosis and targeted therapy. This study evaluates the prognostic value of exosomal miR-122-5p and gut microbiota in HCC patients treated with sorafenib. A total of 180 HCC patients (Child-Pugh A/B, BCLC stage B/C) were prospectively enrolled. Plasma exosomal miR-122-5p levels were quantified by qRT-PCR, while stool samples underwent 16S rRNA sequencing. Clinical outcomes included Overall Survival (OS), Progression-Free Survival (PFS), and sorafenib response.

Results: Exosomal miR-122-5p levels correlated with tumor size (r=0.32, p < 0.001), AFP levels (r=0.28, p=0.003), and microvascular invasion (MVI) (OR=2.14, 95% CI: 1.23–3.72, p=0.007). High miR-122-5p (> median) was associated with shorter OS (HR=2.31, 95% CI: 1.45–3.68, p < 0.001) and PFS (HR=1.89, 95% CI: 1.12–3.18, p=0.017) in multivariate analysis (Table 1). Gut microbiota analysis identified Bacteroides fragilis and Enterococcus faecalis as enriched in non-responders to sorafenib. High B. fragilis abundance was associated with reduced OS (HR=2.05, 95% CI: 1.28–3.28, p=0.004) and PFS (HR=1.78, 95% CI: 1.09–2.90, p=0.021). Combined miR-122-5p and B. fragilis improved prognostic accuracy (C-index=0.79 vs. 0.68 for single markers,p=0.002) (Table 2). In sorafenib-treated patients, the combination of high miR-122-5p and B. fragilis predicted poor response (OR=4.32, 95% CI: 2.11–8.85,p < 0.001), with median OS of 8.2 months vs. 15.6 months in low-risk groups (Table 3).

Conclusion: Exosomal miR-122-5p and B. fragilis are independent prognostic biomarkers for HCC. Their combination enhances prediction of sorafenib response and survival, offering opportunities for personalized precision medicine.