Abstract 1962: Identifying microRNA panels specifically associated with hepatocellular carcinoma and its different etiologies
Authors: Shen Jing , Siegel Abby B. , Remotti Helen , Wang Qiao , Santella Regina M. 
Published: July 2016

Hepatocellular carcinoma (HCC) incidence in the US has increased dramatically due to hepatitis C virus (HCV) infection and the epidemic of obesity-related nonalcoholic fatty liver disease (NAFLD). Many microRNAs (miRNAs) have been identified as deregulated in HCC, but few results are consistent in previous studies. In the current study, we integrate clinical and etiologic data, as well as miRNA profiles from HCC and other 8 types of solid tumors from The Cancer Genome Atlas (TCGA) and Columbia University Medical Center (CUMC) data to investigate “HCC tumor type specific” and “tumor common” miRNA panels. Aberrant miRNA panels associated with HCCs of different etiology were also explored. 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, we well classified HCC tumor tissues with 4 misclassifications among 48 paired tissues. Validating this panel in an additional 302 HCC tumor tissues, we 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, we observed 40 miRNAs significantly deregulated in HCC with over 2-fold changes; 14 overlapped with those identified in TCGA. Eight miRNAs were further examined by quantitative RT-PCR in 66 paired HCC tissues from CUMC; 7 out of the 8 miRNAs showed consistent fold-changes. 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 HBV- and HCV-related HCC, respectively. By comparison with the other 8 types of solid tumors, our 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 were identified as “tumor common” markers including up-regulated miR-21, miR-182, miR-183, and down-regulated miR-139, miR-144, miR-101-2, miR-451, miR-486. These findings indicate that aberrant miRNA panels have HCC “tumor type specificity” and may be affected by different etiologies. These candidate miRNAs can be used as markers to improve clinical early diagnosis of HCC subtypes with specific etiologies and for more precise prevention and therapy.

Citation Format: Jing Shen, Abby B. Siegel, Helen Remotti, Qiao Wang, Regina M. Santella. Identifying microRNA panels specifically associated with hepatocellular carcinoma and its different etiologies. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1962.