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Original Article

Identifying microRNA panels specifically associated with

hepatocellular carcinoma and its different etiologies

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Jing Shen , Abby B. Siegel , Helen Remotti , Qiao Wang , Regina M. Santella 1
1 Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University Medical Center, New York, NY 10032, USA.
2 Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.
3 Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.

ABSTRACT
Aim: 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. Methods: 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). Results: 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. Conclusion: The authors
concluded that aberrant miRNA panels have HCC “tumor type specificity” and may be affected by etiologic factors.

Key words: MicroRNA; hepatocellular carcinoma; etiologies; The Cancer Genome Atlas

Address for correspondence:
Dr. Jing Shen, Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University Medical Center, 650 W. 168th St. Black
Building Rm.1608, New York, NY 10032, USA. E-mail: js2182@cumc.columbia.edu
Received: 17-12-2015, Accepted: 10-04-2016

Dr. Jing Shen is an Assistant Professor of Environmental Health Sciences at the Columbia University
Medical Center. His research interests focus on epigenetic (DNA methylation, microRNAs, long non-coding
RNAs) and genetic (DNA repair capacity, telomere length) biomarkers and their potential etiological roles in
tumorigenesis. He is also interested in exploring environmental exposure markers (oxidative stress, Aflatoxin
B1, and polycyclic aromatic hydrocarbon (PAH) -DNA, -albumin adducts) in cancer susceptibility, cancer early
diagnosis and survival prediction.

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How to cite this article: Shen J, Siegel AB, Remotti H, Wang Q,
DOI: Santella RM. Identifying microRNA panels specifically associated with
10.20517/2394-5079.2015.66 hepatocellular carcinoma and its different etiologies. Hepatoma Res
2016;2:151-62.

© 2016 Hepatoma Research | Published by OAE Publishing Inc. 151