Case Control Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 28, 2015; 21(44): 12605-12611
Published online Nov 28, 2015. doi: 10.3748/wjg.v21.i44.12605
Studied microRNA gene expression in human hepatocellular carcinoma by microRNA microarray techniques
Jian-Xiang Niu, Xing-Kai Meng, Jian-Jun Ren
Jian-Xiang Niu, Xing-Kai Meng, Jian-Jun Ren, Department of General Surgery of the Affiliated Hospital of Inner Mongolia Medical University, Huhehaote 010010, Inner Mongolia Autonomous Region, China
Author contributions: Niu JX and Ren JJ designed the research; Niu JX and Meng XK performed the research; Niu JX contributed new reagents; Meng XK contributed analytical tools; Niu JX and Ren JJ analyzed the data; Niu JX wrote the paper.
Supported by Inner Mongolia Medical College Millions of Science and Technology Project in 2011, No. NY2011bw004; the 2010 Inner Mongolia Health Bureau of Medical and Health Research Project, No. 2010038; Scientific Research Projects of the Inner Mongolia Autonomous Region High School in 2013, No. NJZY13416.
Institutional review board statement: This study was approved by the Medical Ethics Committee of Inner Mongolia Medical College.
Informed consent statement: All patients involved had previously provided their written, informed consent to have their clinical and pathogenic information used for research.
Conflict-of-interest statement: There was no conflict of interest for any of the authors.
Data sharing statement: There was no discussion of data sharing or its implications for the study participants.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Jian-Jun Ren, Department of General Surgery of the Affiliated Hospital of Inner Mongolia Medical University, No. 42 Zhaowuda Road, Saihan Region, Huhehaote 010010, Inner Mongolia Autonomous Region, China. renjianjunzml@163.com
Telephone: +86-471-3280800
Received: May 24, 2015
Peer-review started: May 25, 2015
First decision: June 25, 2015
Revised: July 26, 2015
Accepted: October 12, 2015
Article in press: October 13, 2015
Published online: November 28, 2015
Abstract

AIM: To achieve a better understanding of the molecular mechanisms of microRNA expression changes involved in hepatocellular carcinoma.

METHODS: In this research process, patients were not treated with antivirals, immunosuppressants or immunomodulators for at least 6 mo before collecting serum. The study population was composed of 35 outpatient hepatitis B virus (HBV) cases and 12 healthy control cases from the Affiliated Hospital of Inner Mongolia Medical University (Inner Mongolia, China) from July 2013 to April 2014. The 35 HBV cases were divided into two groups: a hepatocirrhosis group with 20 cases and a liver cancer group with 15 cases. All 35 cases carried HBsAg. The diagnostic criteria followed the European Association for the Study of the Liver 2012 (EASL2012) standards. MicroRNA (miRNA) was extracted from a control group of patients, a group with hepatocirrhosis and a group with liver cancer and its quality was analyzed using the human V2 microRNA expression beadchip. Cluster analysis and a radar chart were then applied to the miRNA changes.

RESULTS: The miRNA-qualified rate of human serum samples was 93%. The concentration of a single sample was > 200 ng/μL and the volume was > 5 μL. All miRNA serum samples were uncontaminated by the genome. The Mann-Whitney test showed significant differences in miRNA between each group, with a detection P-value of < 0.05. Illumina software was set up with Diff Score set to ± 13, meaning that P = 0.001.There were significant changes in miRNA expression between the three groups. miRNA-183 was the most up-regulated, followed by miRNA-373. miRNA-129 and miRNA-188 were both strongly down-regulated and miRNA-378 was down-regulated a small amount. The liver cancer group had greater changes, which indicated that changes in miRNA expression levels were caused by hepatocirrhosis. The liver cancer disease course then further increased these changes. In the pentagon created by these five miRNAs, three groups showed significant deviation. The liver cancer group had a bigger deviation trend. The chart indicated that miRNA expression changes occurred in the hepatocirrhosis group, which increased in the liver cancer disease course and were irreversible.

CONCLUSION: There was a significant relationship between the irreversible up-regulation of miRNA-183/373 and down-regulation of miRNA-129/188/378 and incidences of hepatocirrhosis and liver cancer.

Keywords: Hepatocellular carcinoma, MicroRNA, Expression, Microarray technologies, Radar chart

Core tip: There was a better understanding of the molecular mechanisms of microRNA (miRNA) expression changes involved in hepatocellular carcinoma, associated patients with aggressive malignancy and poor prognosis. The 35 hepatitis B virus cases were divided into two groups, a hepatocirrhosis group with 20 cases and a liver cancer group with 15 cases. 12 healthy people were used as a control. There were significant changes in miRNA expression between the three groups. miRNA-183 was the most up-regulated, followed by miRNA-373. miRNA-129 and miRNA-188 were both strongly down-regulated and miRNA-378 was down-regulated a small amount. The liver cancer group had greater changes, which indicated that changes in miRNA expression levels were caused by hepatocirrhosis. The liver cancer disease course then further increased these changes.