Diagnostic accuracy of DNA methylation in detection of gastric cancer: a meta-analysis

Weiling Hu, Wenfang Zheng, Qifang Liu, Hua Chu, Shujie Chen, John J Kim, Jiaguo Wu, Jianmin Si, Weiling Hu, Wenfang Zheng, Qifang Liu, Hua Chu, Shujie Chen, John J Kim, Jiaguo Wu, Jianmin Si

Abstract

Emerging studies demonstrate the diagnostic utility of DNA methylation-based blood test for gastric cancer. The aim of the meta-analysis is to evaluate the accuracy of blood DNA methylation markers for detecting patients with gastric cancer. A systematic literature search to November 2016 that evaluated DNA methylation markers utilizing blood specimen to detect gastric cancer were selected to derive pooled sensitivities and specificities. 32 studies including 4,172 patients (gastric cancer (N = 2,098), control (N = 2,074)) met the study criteria. Overall sensitivity of DNA methylation-based blood test for detecting gastric cancer was 57% (95% CI 50-63%); specificity was 97% (95% CI 95-98%). Among patients who received plasma-based testing, sensitivity was 71% (95% CI 59-81%); specificity was 89% (95% CI 78-94%). Among patients who received serum-based testing, sensitivity was 50% (95% CI 43-58%); specificity was 98% (95% CI 96-99%). Using multiple methylated genes had sensitivity of 76% (95% CI 64-84%); specificity of 85% (95% CI 65-95%). DNA methylation test had sensitivity of 55% (95% CI 47-64%) and specificity of 96% (95% CI 92-98%) for detecting TNM stage I+II gastric cancer. In conclusion, blood-based DNA methylation test had high specificity but modest sensitivity for detecting gastric cancer. Evaluating multiple methylated genes or using plasma sample may improve the diagnostic sensitivity.

Keywords: DNA methylation; blood; diagnosis; gastric cancer; non-invasive.

Conflict of interest statement

CONFLICTS OF INTEREST Authors have no conflicts of interest to declare.

Figures

Figure 1. Flow diagram of studies identified…
Figure 1. Flow diagram of studies identified in the meta-analysis
Figure 2
Figure 2
Forest plot of individual study and pooled sensitivities (A) and specificities (B) of blood DNA methylation marker for detection of gastric cancer.
Figure 3. Summary ROC curve with confidence…
Figure 3. Summary ROC curve with confidence intervals and prediction regions around mean operating sensitivity and specificity points for detection of gastric cancer
Figure 4. Forest plots of multivariable meta-regression…
Figure 4. Forest plots of multivariable meta-regression and subgroup analysis for sensitivity and specificity
Figure 5. Overall quality assessment of included…
Figure 5. Overall quality assessment of included studies (QUADAS-2 tool)
Figure 6
Figure 6
Deeks’ funnel plot asymmetry test to assess publication bias in estimates of diagnostic odds ratio for (A) plasma-based testing, (B) presence of multiple DNA methylation markers.

References

    1. Fitzmaurice C, Dicker D, Pain A, Hamavid H, Moradi-Lakeh M, MacIntyre MF, Allen C, Hansen G, Woodbrook R, Wolfe C, Hamadeh RR, Moore A, Werdecker A, et al. The Global Burden of Cancer 2013. JAMA Oncol. 2015;1:505–527.
    1. Qi Q, Pan YF, Shen JJ, Gu XQ, Han SW, Liao HH, Jiang YZ, Zhong LP. Circulating DNA for detection of gastric cancer. Eur Rev Med Pharmacol Sci. 2016;20:2558–2564.
    1. Tanzer M, Liebl M, Quante M. Molecular biomarkers in esophageal, gastric, and colorectal adenocarcinoma. Pharmacol Ther. 2013;140:133–147.
    1. Yu J, Zhang S, Zhao B. Differences and correlation of serum CEA, CA19–9 and CA72-4 in gastric cancer. Mol Clin Oncol. 2016;4:441–449.
    1. Wada N, Kurokawa Y, Miyazaki Y, Makino T, Takahashi T, Yamasaki M, Nakajima K, Takiguchi S, Mori M, Doki Y. The characteristics of the serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels in gastric cancer cases. Surg Today. 2016;47:1–6.
    1. Liang Y, Wang W, Fang C, Raj SS, Hu WM, Li QW, Zhou ZW. Clinical significance and diagnostic value of serum CEA, CA19-9 and CA72-4 in patients with gastric cancer. Oncotarget. 2016;7:49565–49573. .
    1. Qu Y, Dang S, Hou P. Gene methylation in gastric cancer. Clin Chim Acta. 2013;424:53–65.
    1. How KA, Nielsen HM, Tost J. DNA methylation based biomarkers: practical considerations and applications. Biochimie. 2012;94:2314–2337.
    1. Shames DS, Minna JD, Gazdar AF. DNA methylation in health, disease, and cancer. Curr Mol Med. 2007;7:85–102.
    1. Zou XP, Zhang B, Zhang XQ, Chen M, Cao J, Liu WJ. Promoter hypermethylation of multiple genes in early gastric adenocarcinoma and precancerous lesions. Hum Pathol. 2009;40:1534–1542.
    1. Shivapurkar N, Gazdar AF. DNA methylation based biomarkers in non-invasive cancer screening. Curr Mol Med. 2010;10:123–132.
    1. Liu L, Yang X. Implication of Reprimo and hMLH1 gene methylation in early diagnosis of gastric carcinoma. Int J Clin Exp Pathol. 2015;8:14977–14982.
    1. Chen X, Lin Z, Xue M, Si J, Chen S. Zic1 Promoter Hypermethylation in Plasma DNA Is a Potential Biomarker for Gastric Cancer and Intraepithelial Neoplasia. PLoS One. 2015;10:e0133906.
    1. Cheung KF, Lam CN, Wu K, Ng EK, Chong WW, Cheng AS, To KF, Fan D, Sung JJ, Yu J. Characterization of the gene structure, functional significance, and clinical application of RNF180, a novel gene in gastric cancer. Cancer. 2012;118:947–959.
    1. McCabe DC, Caudill MA. DNA methylation, genomic silencing, and links to nutrition and cancer. Nutr Rev. 2005;63:183–195.
    1. Liu JB, Wu XM, Cai J, Zhang JY, Zhang JL, Zhou SH, Shi MX, Qiang FL. CpG island methylator phenotype and Helicobacter pylori infection associated with gastric cancer. World J Gastroenterol. 2012;18:5129–5134.
    1. Qian LY, Zhang W. The diagnostic value of DNA hypermethylation in stool for colorectal cancer: a meta-analysis. J Cancer Res Ther. 2014;10:287–291.
    1. Chen H, Yu Y, Rong S, Wang H. Evaluation of diagnostic accuracy of DNA methylation biomarkers for bladder cancer: a systematic review and meta-analysis. Biomarkers. 2014;19:189–197.
    1. Ji X, Guan C, Jiang X, Li H. Diagnostic accuracy of DNA methylation for head and neck cancer varies by sample type and number of markers tested. Oncotarget. 2016;7:80019–80032. .
    1. Shimada H, Noie T, Ohashi M, Oba K, Takahashi Y. Clinical significance of serum tumor markers for gastric cancer: a systematic review of literature by the Task Force of the Japanese Gastric Cancer Association. Gastric Cancer. 2014;17:26–33.
    1. Huang YK, Yu JC, Kang WM, Ma ZQ, Ye X, Tian SB, Yan C. Significance of Serum Pepsinogens as a Biomarker for Gastric Cancer and Atrophic Gastritis Screening: A Systematic Review and Meta-Analysis. PLoS One. 2015;10:e0142080.
    1. Xue WJ, Feng Y, Wang F, Li P, Liu YF, Guo YB, Wang ZW, Mao QS. The value of serum RASSF10 hypermethylation as a diagnostic and prognostic tool for gastric cancer. Tumour Biol. 2016;37:11249–11257.
    1. Liu L, Wang S, Cao X, Liu J. Diagnostic value of circulating microRNAs for gastric cancer in Asian populations: a meta-analysis. Tumour Biol. 2014;35:11995–12004.
    1. Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB. Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA. 1996;93:9821–9826.
    1. Kurdyukov S, Bullock M. DNA Methylation Analysis: Choosing the Right Method. Biology (Basel) 2016:5.
    1. Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, Leeflang MM, Sterne JA, Bossuyt PM. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155:529–536.

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