Identifying microRNA panels speciifcally associated with hepatocellular carcinoma and its different etiologies

摘要

Aim: Deregulation of microRNAs (miRNAs) expression has been identiifed in hepatocelular carcinoma (HCC), but few results are consistent. The objective of this study is to investigate “HCC tumor type speciifc” and “tumor common” miRNA panels.Methods: The authors integrate and analyze clinical, etiologic and miRNA proifles data from 9 types of solid tumors in The Cancer Genome Atlas (TCGA) and HCC data from Columbia University Medical Center (CUMC).Results: Levels of 33 miRNAs were signiifcant different between HCC tumor and paired non-tumor tissues (over 2-fold changes) after Bonferroni correction for multiple comparisons, and most (28 miRNAs) were down-regulated in HCC tumors. Using this panel, the authors wel classiifed HCC tumor tissues with 4 misclassiifcations among 48 paired tissues. Validating this panel in an additional 302 HCC tumor tissues, the authors almost perfectly distinguished tumor from non-tumor tissues with only two misclassiifcations (99% of HCC tissues correctly classiifed). Evaluating miRNA proifles in 32 independent HCC paired tissues from CUMC, the authors observed 40 miRNAs signiifcantly deregulated in HCC with over 2-fold changes; 14 overlapped with those identiifed in TCGA. Subgroup analyses by HCC etiology found that 4 upregulated and 8 downregulated miRNAs were signiifcantly associated with alcohol-related HCC. There were 7 and 4 miRNAs signiifcantly associated with hepatitis B virus- and hepatitis C virus-related HCC, respectively. Data for the ifrst time revealed that miR-24-1, miR-130a and miR-505 were signiifcantly down-regulated only in HCC tumors; miR-142 and miR-455 were signiifcantly down-regulated in HCC, but up-regulated in 5 other solid tumors; suggesting their HCC “tumor type speciifc” characteristics. A panel of 8 miRNAs was signiifcant in at least 5 tumor types, including HCC, and was identiifed as “tumor common” marker.Conclusion: The authors concluded that aberrant miRNA panels have HCC “tumor type speciifcity” and may be affected by etiologic factors.