Correlation of DAPK1 methylation and the risk of gastrointestinal cancer: A systematic review and meta-analysis

Wenzheng Yuan; Jinhuang Chen; Yan Shu; Sanguang Liu; Liang Wu; Jintong Ji; Zhengyi Liu; Qiang Tang; Zili Zhou; Yifeng Cheng; Bin Jiang; Xiaogang Shu

doi:10.1371/journal.pone.0184959

Correlation of DAPK1 methylation and the risk of gastrointestinal cancer: A systematic review and meta-analysis

PLoS One. 2017 Sep 21;12(9):e0184959. doi: 10.1371/journal.pone.0184959. eCollection 2017.

Authors

Wenzheng Yuan¹, Jinhuang Chen², Yan Shu³, Sanguang Liu⁴, Liang Wu¹, Jintong Ji¹, Zhengyi Liu¹, Qiang Tang¹, Zili Zhou¹, Yifeng Cheng¹, Bin Jiang⁵, Xiaogang Shu¹

Affiliations

¹ Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
³ College of Clinical Medicine, Hubei University of Science and Technology, Xianning, China.
⁴ Department of Hepatobiliary Surgery, The Second Hospital, Hebei Medical University, Shijiazhuang, China.
⁵ Department Breast & Thyroid Surgery, TongJi Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Abstract

Objective: One of the critical mechanisms of gastrointestinal cancer pathogenesis is the silencing of death associated protein kinase 1 (DAPK1), which could be caused by aberrant methylation of the promoter. However, the relationship between DAPK1 methylation and the risk of gastrointestinal cancer is still controversial. Hence, we conducted this study to determine the potential correlation.

Methods: Eligible publications were searched in the Pubmed, Embase, and Cochrane Library through November 2016 according to the inclusion criteria and exclusion criteria. Revman 5.3 and Stata 12.0 software were used to analyze the relevant data regarding the association between the frequency of DAPK1 methylation and gastrointestinal cancer.

Results: A total of 22 studies with 2406 patients were included in this meta analysis. Methylation of DAPK1 was positively related with the risk of gastrointestinal cancer (odds ratio [OR] = 5.35, 95% confidence interval [CI]: 2.76-10.38, P<0.00001, random effects model). The source of heterogeneity was analyzed by sensitivity analysis and subgroup analysis. After omitting one heterogeneous study, the I2 decreased and the OR increased in pooled analysis. Also, the heterogeneity decreased most significantly in the subgroup of studies that had a sample size of less than 60 cases. Then, the correlations between DAPK1 methylation and clinicopathological features of gastrointestinal cancer were assessed. DAPK1 methylation was positively correlated with the lymph node (N) stage (positive vs. negative, OR = 1.45, 95%CI: 1.01-2.06, P = 0.04, fixed effects model) and poor differentiation (OR = 1.55, 95%CI: 1.02-2.35, P = 0.04, fixed effects model) in gastric cancer, and the association was significant among Asian patients. However, among cases of gastrointestinal cancer, the association between DAPK1 methylation and tumor (T) stage, N stage, distant metastasis (M) stage, and cancer differentiation were not statistically significant.

Conclusions: DAPK1 methylation is a potential biomarker for the early diagnosis of gastrointestinal cancer. Further analysis of the clinicopathological features indicated that aberrant methylation of DAPK1 is positively associated with the tumorigenesis of gastrointestinal cancer, and metastasis of gastric cancer.

Publication types

Meta-Analysis
Review
Systematic Review

MeSH terms

DNA Methylation*
Death-Associated Protein Kinases / genetics*
Gastrointestinal Neoplasms / genetics*
Gene Expression Regulation, Neoplastic
Genetic Predisposition to Disease*
Humans
Risk Factors

Substances

DAPK1 protein, human
Death-Associated Protein Kinases

Grants and funding

This study was supported by the National Nature Science Foundation of China (No. 81470789 and 81271199) (http://www.nsfc.gov.cn/), and Research Fund of Public welfare in Health Industry (No. 201402015), Health and Family Plan Committee of China, 2014 (http://www.nhfpc.gov.cn/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.