Observational Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 21, 2016; 22(7): 2373-2382
Published online Feb 21, 2016. doi: 10.3748/wjg.v22.i7.2373
CD24 genetic variants contribute to overall survival in patients with gastric cancer
Zhi-Fang Jia, Li-Zhong Wang, Xue-Yuan Cao, Chuan Wang, Dong-Hui Cao, Xing Wu, Li-Li You, Mei-Shan Jin, Yin-Ping Wang, Bao-Sen Zhou, Jing Jiang
Zhi-Fang Jia, Chuan Wang, Dong-Hui Cao, Xing Wu, Li-Li You, Jing Jiang, Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Li-Zhong Wang, Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, United States
Xue-Yuan Cao, Department of Gastrointestinal Surgery, First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Mei-Shan Jin, Yin-Ping Wang, Division of Pathology, First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Zhi-Fang Jia, Bao-Sen Zhou, Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110112, Liaoning Province, China
Author contributions: Jia ZF, Wang LZ, Cao XY and Jiang J designed the research; Jia ZF, Wang C, Cao DH, Wu X and You LL performed the research; Wang LZ, Cao XY, Jin MS and Wang YP analyzed the data; Jia ZF and Jiang J wrote the manuscript; Wang LZ, Cao XY and Zhou BS revised the manuscript.
Supported by National Natural Science Foundation of China, No. 81373084 and No. 81273065; the Norman Bethune Program of Jilin University, No. 2013025; and the Youth Fund of the First Hospital of Jilin University, No. JDYY42013014.
Institutional review board statement: The study was reviewed and approved by the ethics committee of the First Hospital of Jilin University.
Informed consent statement: All the participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors declare no conflicts of interest.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at jiangjing19702000@jlu.edu.cn.
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: Jing Jiang, MD, PhD, Division of Clinical Epidemiology, First Hospital of Jilin University, 71 Xinmin Street, Changchun 130021, Jilin Province, China. jiangjing19702000@jlu.edu.cn
Telephone: +86-431-81875408 Fax: +86-431-85654528
Received: May 11, 2015
Peer-review started: May 12, 2015
First decision: July 19, 2015
Revised: August 12, 2015
Accepted: November 30, 2015
Article in press: November 30, 2015
Published online: February 21, 2016
Abstract

AIM: To investigate the role of single nucleotide polymorphisms (SNPs) in CD24 gene in susceptibility and overall survival of gastric cancer (GC).

METHODS: We genotyped 3 tagging SNPs of CD24-P-534 in the promoter region, P170 in the coding region of exon 2 and P1527 in the 3′ untranslated region - using polymerase chain reaction-restriction fragment length polymorphism in specimens from 679 histologically-confirmed GC cases, 111 gastric atrophy (GA) cases and 976 tumor-free controls. Serum immunoglobulin G antibodies to Helicobacter pylori (H. pylori) of all subjects were detected by enzyme-linked immunosorbent assay. CD24 expression was evaluated by immunohistochemistry in 131 GC specimens. Correlations between SNPs and risk of GC or GA were shown by P values and odd ratios (ORs) with 95% confidence intervals (95%CI) compared with the most common genotype of each SNP using the unconditional logistic regression model after adjusting for age, sex and H. pylori infection. Survival within each SNP group was plotted by Kaplan-Meier method and compared by log-rank test (recessive model). Hazard ratios with 95%CIs were computed by Cox regression model after adjusting for age, sex, histological type, tumor differentiation, clinical stage and post-operational chemotherapy.

RESULTS: All of the three loci were in Hardy-Weinberg equilibrium in the control group. Median follow-up time for the 600 GC patients included in the survival analysis was 36.2 mo (range, 2.1-66.7 mo; 95%CI: 34.3-36.5 mo). Patients with the P-534 A/A genotype had significantly shorter survival (HR = 1.38, 95%CI: 1.01-1.88, P = 0.042) than did the C/C or C/A genotype carriers after adjusting for age, sex, histological type, tumor differentiation, clinical stage and post-operational chemotherapy. This trend was more evident in patients who lived longer than 2.5 years (HR = 7.55, 95%CI: 2.16-26.32, P = 0.001). The P170 T/T genotype was associated with a shorter lifespan than the non-T/T genotypes, but not significantly so. None of the three genetic variants was found to be associated with risk of GC (including tumor stage, grade and distant metastasis) or with risk of gastric atrophy. Furthermore, no difference of CD24 expression was found among the genotypes.

CONCLUSION: The P-534 site in CD24 gene affects the overall survival of gastric cancer and may serve as a prognostic marker for gastric cancer.

Keywords: Gastric cancer, CD24, Single nucleotide polymorphisms, Gastric atrophy, Overall survival

Core tip: We evaluated the role of three genetic variants of CD24 in gastric cancer (GC) risk and prognosis using 679 GC cases and 976 controls. We observed that GC cases with the A/A genotype of P-534 (which lies in the CD24 promoter) had a significantly shorter survival (HR = 1.38) especially among patients who lived longer than 2.5 years (HR = 7.55) after adjusting for age, sex, histological type, tumor differentiation, clinical stage and post-operational chemotherapy. Our study provides the first evidence that P-534 site in CD24 may serve as a prognostic marker for gastric cancer.