Reply to G. Cai et al

Abstract

We would like to thank Cai et al for their comments on our article. In the study by Gao et al, microRNA (miRNA) was extracted from formalin-fixed, paraffin-embedded dysplastic nodules, hepatocellular carcinomas (HCCs), and the adjacent nontumorous liver tissues. This study showed that miRNA deregulation at the tissue level was an early event and accumulated throughout the various steps of hepatitis B virus–associated hepatocarcinogenesis. In our study, the panel with seven miRNAs (miR-122, miR-192, miR-21, miR-223, miR-26a, miR-27a, and miR-801) was identified in the plasma of patients with HCC. The discrepancy between the two studies would be primarily a result of the different categories of the study specimens (tissue v plasma). To our knowledge, the expression profiles of plasma miRNA are different from that of tissue miRNA. Plasma circulating miRNA was reported to have diverse origins. It is well known that most hepatitis B virus–related HCCs involve two disease processes: the HCC as well as liver damage as a result of either hepatitis or cirrhosis. Thus, liver damage, tumor immune response, and/or hepatitis may also influence the miRNA profiles in the plasma of patients with HCC. Therefore, the expression profiles of plasma miRNAs in patients with HCC may not trend according to the expression profiles in HCC tissue. For example, studies by Wang et al and Starkey Lewis et al found miR-122 and miR-192 to be associated with liver damage, and the two miRNAs expressed opposite regulations in the tissue and plasma specimens. This indicates that the miRNA profiles in the plasma specimens are more complicated compared with those in pure tumor tissue in patients with HCC. At the tissue level, two studies revealed the differences in miRNA dysregulation in early versus advanced HCCs. Such differences have not been reported in the current plasma studies of miRNA profiles. It would be interesting to further investigate the differences in miRNA spectrum and expression level between early and advanced HCCs in the plasma of patients with HCC.