title: Accumulated promoter methylation as a potential biomarker for esophageal cancer.
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.
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.|Department of Public Health and Preventive Medicine, Kangda College of Nanjing Medical University, Lianyungang, 222000, China.
authors.forename: Xianzhen
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Thoracic Surgery, People's Hospital of Yangzhong, Yangzhong, 212200, China.
authors.forename: Hengchuan
authors.initials: H
authors.lastname: Xue
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Lingshuang
authors.initials: L
authors.lastname: Lü
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Peiyi
authors.initials: P
authors.lastname: Shi
authors.affiliation: Department of Thoracic Surgery, People's Hospital of Yangzhong, Yangzhong, 212200, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.|Department of Social Medicine and Health Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.|The Innovation Center for Social Risk Governance in Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Wang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D019295:Computational Biology / Q000379:methods; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic
chemical_list: D014408:Biomarkers, Tumor
keywords: diagnosis; epigenetics; esophageal cancer; methylation; next-generation sequencing