Circulating miR-148/152 family as potential biomarkers in hepatocellular carcinoma

Aberrant expressions of the miR-148/152 family (miR-148a, miR-148b, and miR-152) have been documented in many tumor tissues, including hepatocellular carcinoma (HCC). However, the expression pattern and clinical significance of circulating miR-148/152 family in HCC remain elusive. In this study, we conducted quantitative real-time polymerase chain reaction (qRT-PCR) to examine the levels of serum miR-148a, miR-148b, and miR-152 in 76 HCC cases, as well as 62 controls with benign liver diseases and 55 healthy volunteers. Our results showed that serum levels of three microRNAs (miRNAs) were significantly decreased in HCC cases than those in benign and healthy controls (all P < 0.05). Moreover, they showed strong correlations with each other in HCC group (r = 0.6716, 0.5381, and 0.7712; all P < 0.001). Receiver operating characteristic (ROC) analysis revealed that the combination of circulating miR-148/152 family had an increased area under the curve (AUC) = 0.940 (95 % confidence interval (CI), 0.886-0.973) with the sensitivity of 96.1 % and the specificity of 91.9 %, which were significantly higher than those of serum alpha-fetoprotein (AFP) and three miRNAs alone in differentiating HCC from benign liver diseases. In addition, serum miR-148a and miR-148b were significantly associated with tumor size (P = 0.011 and 0.037) and tumor-node-metastasis (TNM) stage (P < 0.001 and P = 0.034), yet serum miR-152 was only correlated with TNM stage (P = 0.009). Also, dynamic monitoring three miRNAs can help us predict recurrence or metastasis in HCC cases after surgical resection. Besides, Kaplan-Meier analyses demonstrated that the decreased serum miR-148a (P < 0.001) and miR-152 (P = 0.012) was closely correlated with shorten overall survival of HCC patients. Additionally, Cox regression model further indicated that serum miR-148a was strongly associated with the prognosis of HCC patients. Our study suggests that downregulated circulating miR-148/152 family can provide positive diagnostic value for HCC. Moreover, serum miR-148a might be as independent prognostic factor for HCC patients.