Serum exosomal microRNA-122 and microRNA-21 as predictive biomarkers in transarterial chemoembolization-treated hepatocellular carcinoma patients

摘要

Exosomal microRNAs (miRNAs) have been investigated as potential novel biomarkers, and miR-122 and miR-21 were shown to be important in hepatocellular carcinoma (HCC). We analyzed the importance of serum exosomal miRNA expression levels in HCC patients that underwent transarterial chemoembolization (TACE). Seventy-five HCC patients who underwent TACE as the initial treatment in Nagasaki University Hospital were enrolled. Exosomal miRNAs were isolated from serum samples collected before and after TACE. Exosomal miR-122 expression levels significantly decreased after TACE (P=0.012), while the exosomal miR-21 expression levels did not significantly change. The expression levels of exosomal miR-122 before TACE were shown to correlate significantly with aspartate aminotransferase (r=0.31, P=0.004) and alanine aminotransferase (r=0.33, P=0.003) levels, tumor diameter (r=0.29, P=0.010) and Child-Pugh score (r=−0.28, P=0.013). The median survival time for all patients was 47 months, and neither of the investigated exosomal miRNAs were shown to be independent factors associated with the disease-specific survival. According to the median relative expression of miR-122 after TACE/before TACE (miR-122 ratio) in liver cirrhosis patients (n=57), the patients with a higher miR-122 ratio had significantly longer disease-specific survival, compared with that of the patients with the lower miR-122 ratio (P=0.0461). Multivariate Cox proportional hazards regression analysis of clinical parameters revealed that a lower exosomal miR-122 ratio (HR 2.720; 95% confidence interval, 1.035–8.022; P=0.042) is associated with the disease-specific survival. Taken together, our results demonstrate that the exosomal miR-122 level alterations may represent a predictive biomarker in HCC patients with liver cirrhosis treated with TACE.