Accumulated promoter methylation as a potential biomarker for esophageal cancer

Xianzhen Peng; Hengchuan Xue; Lingshuang Lü; Peiyi Shi; Jianping Wang; Jianming Wang

doi:10.18632/oncotarget.13510

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Research Papers:

Accumulated promoter methylation as a potential biomarker for esophageal cancer

Xianzhen Peng, Hengchuan Xue, Lingshuang Lü, Peiyi Shi, Jianping Wang and Jianming Wang _

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Oncotarget. 2017; 8:679-691. https://doi.org/10.18632/oncotarget.13510

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Abstract

Xianzhen Peng1,2,*, Hengchuan Xue3,*, Lingshuang Lü1,*, Peiyi Shi1, Jianping Wang3, Jianming Wang1,4,5

1Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, 211166, China

2Department of Public Health and Preventive Medicine, Kangda College of Nanjing Medical University, Lianyungang, 222000, China

3Department of Thoracic Surgery, People’s Hospital of Yangzhong, Yangzhong, 212200, China

4Department of Social Medicine and Health Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China

5The Innovation Center for Social Risk Governance in Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China

*These authors contributed equally to this work

Correspondence to:

Jianming Wang, email: [email protected]

Keywords: esophageal cancer, epigenetics, methylation, next-generation sequencing, diagnosis

Received: July 25, 2016 Accepted: November 14, 2016 Published: November 22, 2016

ABSTRACT

We performed a two-stage molecular epidemiological study to explore DNA methylation profiles for potential biomarkers of esophageal squamous cell carcinoma (ESCC) in a Chinese population. Infinium Methylation 450K BeadChip was used to identify genes with differentially methylated CpG sites. Sixteen candidate genes were validated by sequencing 1160 CpG sites in their promoter regions using the Illumina MiSeq platform. When excluding sites with negative changes, 10 genes (BNIP3, BRCA1, CCND1, CDKN2A, HTATIP2, ITGAV, NFKB1, PIK3R1, PRDM16 and PTX3) showed significantly different methylation levels among cancer lesions, remote normal-appearing tissues, and healthy controls. PRDM16 had the highest diagnostic value with the AUC (95% CI) of 0.988 (0.965–1.000), followed by PIK3R1, with the AUC (95% CI) of 0.969 (0.928–1.000). In addition, the methylation status was higher in patients with advanced cancer stages. These results indicate that aberrant DNA methylation may be a potential biomarker for the diagnosis of ESCC.

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Research Papers:

Accumulated promoter methylation as a potential biomarker for esophageal cancer

Abstract