Serum exosomal miR-125b is a novel prognostic marker for hepatocellular carcinoma

Abstract

Abstract: Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide with high mortality. Circulating miRNA has been demonstrated as a novel noninvasive biomarker for many tumors. This study aimed to investigate the potential of circulating miR-125b as a prognostic marker of HCC. Exosomes were extracted from serum samples collected from two independent cohorts: cohort 1: HCC (n=30), chronic hepatitis B (CHB, n=30), liver cirrhosis (LC, n=30); cohort 2: HCC (n=128). We found that miR-125b levels were remarkably increased in exosomes compared to those in serum from patients with CHB, LC, and HCC ( P <0.01, respectively). However, miR-125b levels in exosomes and the serum from HCC patients were inferior to that of CHB ( P <0.01 and P =0.06) and LC patients ( P <0.01 for all). Additionally, miR-125b levels in exosomes were associated with tumor number ( P =0.02), encapsulation ( P <0.01), and TNM stage ( P <0.01). Kaplan–Meier analysis indicated that HCC patients with lower exosomal miR-125b levels showed reduced time to recurrence (TTR) ( P <0.01) and overall survival (OS) ( P <0.01). Furthermore, multivariate analysis revealed that miR-125b level in exosomes, but not in serum, was an independent predictive factor for TTR ( P <0.001) and OS ( P =0.011). Exosomal miR-125b levels predicted the recurrence and survival of HCC patients with an area under the ROC curve of 0.739 (83.0% sensitivity and 67.9% specificity) and 0.702 (82.5% sensitivity and 53.4% specificity). In conclusion, exosomal miR-125b could serve as a promising prognostic marker for HCC. Keywords: exosome, miR-125b, hepatocellular carcinoma, prognosis, serum