title: DNA Methylation Status of PAX1 and ZNF582 in Esophageal Squamous Cell Carcinoma.
abstract: Hypermethylation of specific gene promoters is an important mechanism of carcinogenesis. A high frequency of promoter methylation ofPAX1andZNF582genes has been detected in cervical cancer. In the present study, we investigated the methylation status ofPAX1andZNF582genes in esophageal squamous cell carcinoma (ESCC) tissues. Tumor and paracancerous tissues were obtained from 14 ESCC patients. Genomic DNA was extracted from both tumor and paracancerous tissues, and the concentration of DNA were determined. DNA methylation analysis ofPAX1andZNF582genes was carried out using quantitative methylation-specific PCR. To assess the diagnostic performance of the two methylated genes for cancer detection, receiver operating characteristic (ROC) curves were generated. Sensitivities and specificities were tested at cut-offs obtained from the ROC curves. The methylation levels of bothPAX1andZNF582genes were significantly higher in tumor tissues compared to non-tumor paracancerous tissues. The methylation rates ofPAX1andZNF582in ESCC tumor and paracancerous tissues were 100% and 21.4% (p= 0.006), 85.7% and 0% (p< 0.001), respectively. The sensitivities and specificities ofPAX1andZNF582methylation for the detection of cancer were 100% and 85.7%, and 78.6% and 100%, respectively. The DNA methylation levels and frequencies ofPAX1andZNF582genes were markedly higher in ESCC tumor tissues compared to those in paracancerous tissues. Moreover, the conclusions were verified by using The Cancer Genome Atlas (TCGA) datasets. DNA methylation status of these two genes showed a relatively good sensitivity and specificity for the detection of ESCC tumors. This data suggests that DNA methylation testing holds a great promise for ESCC screening and warrants further prospective population-based studies.
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, Hunan, China. huangjin879288@163.com.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, Hunan, China. huangjin879288@163.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, Hunan, China. wangguo32@126.com.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, Hunan, China. wangguo32@126.com.
authors.forename: Guo
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, Hunan, China. daratj@163.com.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, Hunan, China. daratj@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Cardiovascular & Thoracic Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China. zhuangweihy@sina.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhuang
authors.affiliation: Department of Clinical Oncology, The First People's Hospital of Chenzhou, Chenzhou 423000, Hunan, China. wlpwlp2005@126.com.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, Hunan, China. yuligh@istat.com.tw.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, Hunan, China. yuligh@istat.com.tw.|iStat Biomedical Co. Ltd., Taipei 221, Taiwan. yuligh@istat.com.tw.
authors.forename: Yu-Ligh
authors.initials: YL
authors.lastname: Liou
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, Hunan, China. yzliu2005@163.com.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, Hunan, China. yzliu2005@163.com.
authors.forename: Ying-Zi
authors.initials: YZ
authors.lastname: Liu
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, Hunan, China. hhzhou2003@163.com.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, Hunan, China. hhzhou2003@163.com.
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, Hunan, China. 212133@csu.edu.cn.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, Hunan, China. 212133@csu.edu.cn.
authors.forename: Yuan-Shan
authors.initials: YS
authors.lastname: Zhu
mesh_terms: D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D019175:DNA Methylation / Q000502:physiology*; D004938:Esophageal Neoplasms / Q000235:genetics*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008875:Middle Aged; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012372:ROC Curve; D012680:Sensitivity and Specificity
chemical_list: D051741:Kruppel-Like Transcription Factors; D051761:Paired Box Transcription Factors; C577358:ZNF582 protein, human; C070835:PAX1 transcription factor
keywords: DNA methylation; PAX1; ZNF582; esophageal squamous cell carcinoma