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

Abstract

Deregulation of microRNAs (miRNAs) expression has been identified in hepatocellular carcinoma (HCC), but few results are consistent. The objective of this study is to investigate "HCC tumor type specific" and "tumor common" miRNA panels. The authors integrate and analyze clinical, etiologic and miRNA profiles data from 9 types of solid tumors in The Cancer Genome Atlas (TCGA) and HCC data from Columbia University Medical Center (CUMC). Levels of 33 miRNAs were significant 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 well classified HCC tumor tissues with 4 misclassifications 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 misclassifications (99% of HCC tissues correctly classified). Evaluating miRNA profiles in 32 independent HCC paired tissues from CUMC, the authors observed 40 miRNAs significantly deregulated in HCC with over 2-fold changes; 14 overlapped with those identified in TCGA. Subgroup analyses by HCC etiology found that 4 upregulated and 8 downregulated miRNAs were significantly associated with alcohol-related HCC. There were 7 and 4 miRNAs significantly associated with hepatitis B virus- and hepatitis C virus-related HCC, respectively. Data for the first time revealed that miR-24-1, miR-130a and miR-505 were significantly down-regulated only in HCC tumors; miR-142 and miR-455 were significantly down-regulated in HCC, but up-regulated in 5 other solid tumors; suggesting their HCC "tumor type specific" characteristics. A panel of 8 miRNAs was significant in at least 5 tumor types, including HCC, and was identified as "tumor common" marker. The authors concluded that aberrant miRNA panels have HCC "tumor type specificity" and may be affected by etiologic factors.