Accumulated promoter methylation as a potential biomarker for esophageal cancer
2017
// Xianzhen Peng 1, 2, * , Hengchuan Xue 3, * , Lingshuang Lu 1, * , Peiyi Shi 1 , Jianping Wang 3 , Jianming Wang 1, 4, 5 1 Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, 211166, China 2 Department of Public Health and Preventive Medicine, Kangda College of Nanjing Medical University, Lianyungang, 222000, China 3 Department of Thoracic Surgery, People’s Hospital of Yangzhong, Yangzhong, 212200, China 4 Department of Social Medicine and Health Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China 5 The 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: jmwang@njmu.edu.cn 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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