These findings indicate that the A to G base change of rs999885 may provide a protective effect against chronic HBV infection but an increased risk for HCC in HBV persistent carriers by altering the expression of the miR-106b-25 cluster.
We conclude that there is aberrant expression of microRNAs encoded by the oncogenic miR-17-92 cluster and the miR-106b-25 cluster in hepatocellular carcinoma.
Over-expression of the miR-106b-25 and miR-17-92 clusters has been reported not only during the development of cirrhosis but also subsequently during the development of hepatocellular carcinoma.
Moreover, the clinical relevance to HCC progression of the combined high miR-106b-5p and low FOG2 expression was more significant than high miR-106b-5p alone.
The results demonstrated that miR-106b was over-expressed in HCC tumor tissue compared with adjacent non-tumor tissue (p = 0.0005), and overexpression of miR-106b was signficantly correlated with higher tumor grade (p = 0.018).
Our previous study showed that the A to G base change of rs999885 may provide an increased risk for HCC in HBV persistent carriers by altering the expression of the miR-106b-25 cluster.
The diagnostic performances of each miRNA and their combinations were measured using Receiver Operating Characteristic (ROC) curve analyses: a classifier consisting of miR-101-3p, miR-1246 and miR-106b-3p produced the best diagnostic precision in plasma of HCC vs. cirrhotic patients (AUC = 0.99).
miR-106b-5p expression was markedly higher in HCC tissues than in noncancerous adjacent liver tissues (P < .001). miR-106b-5p upregulation was significantly associated with advanced TNM stage (P = .02), short recurrence-free (P = .005), and overall (P = .001) survivals.
These observations suggest that the up-regulation of miR-106b by HBeAg contributes to the pathogenesis of HBV-related HCC by down-regulating the Rb gene.
Moreover, the clinical relevance to HCC progression of the combined high miR-106b-5p and low FOG2 expression was more significant than high miR-106b-5p alone.
ROC curves suggested that plasma miR-106b yielded relative high sensitivities and specificities in differentiating HCC patients from CLD patients or healthy controls with corresponding AUC values of 0.726 and 0.879, respectively.