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Huanqiang Wang,Congying Yang,Siyuan Wang,Tian Wang,Jingling Han,Kai Wei,Fucun Liu,Jida Xu,Xianzhen Peng,Jianming Wang.Journal of Biomedical Research,2018,32(6):424-433
Cell-free plasma hypermethylated CASZ1, CDH13 and ING2 are promising biomarkers of esophageal cancer
Received:June 20, 2017  Revised:May 21, 2018
DOI10.7555/JBR.32.20170065
Keywordsesophageal neoplasms, DNA methylation, epigenesist, biological markers, tumor suppressor
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Huanqiang Wang Department of Public Health and Preventive Medicine, Kangda College of Nanjing Medical University, Lianyungang, Jiangsu , China
Congying Yang Department of Pathology, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu , China
Siyuan Wang Department of Clinical Medicine, Kangda College of Nanjing Medical University, Lianyungang, Jiangsu , China
Tian Wang Department of Public Health and Preventive Medicine, Kangda College of Nanjing Medical University, Lianyungang, Jiangsu , China
Jingling Han Department of Public Health and Preventive Medicine, Kangda College of Nanjing Medical University, Lianyungang, Jiangsu , China
Kai Wei Department of Public Health and Preventive Medicine, Kangda College of Nanjing Medical University, Lianyungang, Jiangsu , China
Fucun Liu Department of Public Health and Preventive Medicine, Kangda College of Nanjing Medical University, Lianyungang, Jiangsu , China
Jida Xu Department of Public Health and Preventive Medicine, Kangda College of Nanjing Medical University, Lianyungang, Jiangsu , China
Xianzhen Peng Department of Public Health and Preventive Medicine, Kangda College of Nanjing Medical University, Lianyungang, Jiangsu , China;Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu , China
Jianming Wang Department of Epidemiology, Department of Social Medicine and Health Education, The Innovation Center for Social Risk Governance in Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu , China
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Abstract
      Identifying sensitive and specific biomarkers for early detection of cancer is immensely imperative for early diagnosis and treatment and better clinical outcome of cancer patients. This study aimed to construct a specific DNA methylation pattern of cancer suppressor genes and explore the feasibility of applying cell-free DNA based methylation as a biomarker for early diagnosis of esophageal squamous cell carcinoma (ESCC). We recruited early stage ESCC patients from Yangzhong County, China. The Illumina Infinium 450K Methylation BeadChip was used to onstruct a genome-wide DNA methylation profile. Then, differentiated genes were selected for the validation study using the Sequenom MassARRAY platform. The frequency of methylation was compared between cancer tissues, matched cell-free DNAs and normal controls. The specific methylation profiles were constructed, and the sensitivity and specificity were calculated. Seven CG sites in three genes CASZ1, CDH13 and ING2 were significantly hypermethylated in ESCC as compared with normal controls. A significant correlation was found between the methylation of DNA extracted from cancer tissues and matched plasma cell-free DNA, either for individual CG site or for cumulative methylation analysis. The sensitivity and specificity reached 100% at an appropriate cut-point using these specific methylation biomarkers. This study revealed that aberrant DNA methylation is a promising biomarker for molecular diagnosis of esophageal cancer. Hypermethylation of CASZ1, CDH13 and ING2 detected in plasma cell-free DNA can be applied as a potential noninvasive biomarker for diagnosis of esophageal cancer.
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