Case Control Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 21, 2018; 24(23): 2482-2490
Published online Jun 21, 2018. doi: 10.3748/wjg.v24.i23.2482
Association of twelve polymorphisms in three onco-lncRNA genes with hepatocellular cancer risk and prognosis: A case-control study
Ben-Gang Wang, Qian Xu, Zhi Lv, Xin-Xin Fang, Han-Xi Ding, Jing Wen, Yuan Yuan
Ben-Gang Wang, Qian Xu, Zhi Lv, Xin-Xin Fang, Han-Xi Ding, Jing Wen, Yuan Yuan, Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, Liaoning Province, China
Ben-Gang Wang, Hepatobiliary Surgery Department of General Surgery Institute, the First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Author contributions: Yuan Y conceived and designed this study; Wang BG, Lv Z, Fang XX, and Wen J preformed the experiments; Wang BG, Xu Q, and Ding HX were responsible for the data analysis and performed data interpretation; Wang BG wrote the paper; Lv Z and Yuan Y revised the manuscript.
Supported by the Natural Science Foundation of Liaoning Province in China, No. 20170541001.
Institutional review board statement: The study was approved by the ethics committee of the First Hospital of China Medical University.
Informed consent statement: All patients gave informed consent.
Conflict-of-interest statement: All authors disclose no conflicts of interest that may bias their work.
STROBE statement: The guidelines of the STROBE Statement have been adopted.
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:
Correspondence to: Yuan Yuan, MD, PhD, Professor, Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, No.155 NanjingBei Street, Heping District, Shenyang 110001, Liaoning Province, China.
Telephone: +86-24-83282153 Fax: +86-24-83282383
Received: March 22, 2018
Peer-review started: March 23, 2018
First decision: April 10, 2018
Revised: April 17, 2018
Accepted: May 18, 2018
Article in press: May 18, 2018
Published online: June 21, 2018
Research background

Genetic polymorphisms could be biomarkers for cancer risk and prognosis. Recent years, it was found that coding genes and non-coding genes had single nucleotide polymorphisms (SNPs). LncRNAs had important roles in the tumor incidence, progression, and prognosis. Thus, lncRNA polymorphisms had potential to be biomarkers for cancer precaution and prognostic prediction.

Research motivation

The aim of this study is to screen out the effective biomarkers for the hepatocellular cancer (HCC) risk and prognosis. The selected polymorphisms would have potential for the prediction of cancer risk and prognosis.

Research objectives

Five hundred and twenty-one patients of HCC and frequency matched 817 controls were studied for the cancer risk study. Among them, 351 patients for which the information was all available were recruited for the prognosis study. Then, 68 HCC specimens and corresponding samples from the noncancerous region were detected for the expression level study.

Research methods

For the risk and prognosis study, the samples were detected by the genomic DNA extracted and allele-specific PCR with KASPar reagents. The single nucleotide polymorphisms were selected by the Haploview software. The expression level study isolated the RNA isolated and then converted it to cDNA. The SYBR based real-time PCR were adopted for the lncRNA expression.

Research results

We found the HOTTIP rs17501292, rs2067087, and rs17427960 SNPs increased HCC risk by 1.55-, 1.20-, and 1.18-fold under an allelic model, and the MALAT1 rs4102217 SNP increased HCC risk by 1.32-fold under a dominant model. In addition, the two-way interaction of HOTTIP rs17501292 and MALAT1 rs619586 polymorphisms decreased HCC risk and exhibited epistatic effects. In the survival analysis, the HOTTIP rs3807598 variant genotype showed significantly longer survival time in the hepatitis B virus (HBV)-negative subgroup, and MALAT1 rs591291 showed an association with significantly better prognosis in the female and HBV-negative group. In this study, no significant effect in eQTL analysis was observed.

Research conclusions

Some specific HOTTIP and MALAT1 SNPs have the potential to be biomarkers for HCC risk and prognosis.

Research perspectives

Screening SNPs could be valuable for the identification of biomarkers for HCC risk and prognosis. It could also be used for patient care, as there would be a cohort of patients who would benefit from screening using these positive SNPs.