title: DAPK1, MGMT and RARB promoter methylation as biomarkers for high-grade cervical lesions.
abstract: Gene promoter methylation may be used a potential biomarker for detecting solid tumor including cervical cancer. Here, we used methylation sensitive-high resolution melting (MS-HRM) analysis to detecting promoter methylation ratios of DAPK1, MGMT and RARB gene in patients with different cervical disease grade. The detection of gene promoter methylation was conducted in two hundred fifty patients' samples including normal cytology (n=48), cervical intraepithelial neoplasia grade 1 (CIN1, n=54), cervical intraepithelial neoplasia grade 2 (CIN2, n=47), cervical intraepithelial neoplasia grade 3 (CIN3, n=56) and cervical squamous cell carcinomas (SCS, n=45). We found there were a significant positive correlation between the promoter methylation status of DAPK1 and cervical disease grade (P=0.022). In addition, the methylated promoters of DAPK1 combined with MGMT, MGMT combined with RARB, DAPK1 combined with RARB were positive correlated with cervical disease grade (P < 0.05). All three genes promoters methylated were positive correlated with cervical disease grade (P < 0.001). Receiver operating characteristic (ROC) curves was conducted to evaluate whether the three genes methylation could be used to be a potential marker for diagnosing high grade cervical disease (HSIL and SCC). The cutoff values for the methylation rates of all these genes were 0-5%. Regrettably, only the methylation of MGMT combined with DAPK1 gave 43.4% sensitivity and 68.6% specificity. The current results indicated that MS-HRM-based testing for DNA methylations of MGMT plus DAPK1 genes holds some promise for high grade cervical disease screening.
authors.affiliation: Department of O&G, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science & Peking Union Medical College China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of O&G, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science & Peking Union Medical College China.
authors.forename: Shu
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of O&G, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science & Peking Union Medical College China.
authors.forename: Keng
authors.initials: K
authors.lastname: Shen
authors.affiliation: Fudan University Shanghai Cancer Center, Oncology China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Ye
authors.affiliation: Fudan University Shanghai Cancer Center, Oncology China.
authors.forename: Dongyan
authors.initials: D
authors.lastname: Cao
authors.affiliation: Fudan University Shanghai Cancer Center, Oncology China.
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000032:analysis / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000032:analysis / Q000235:genetics*; D064550:Death-Associated Protein Kinases / Q000032:analysis / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D011401:Promoter Regions, Genetic; D012372:ROC Curve; D018168:Receptors, Retinoic Acid / Q000032:analysis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology*; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D018168:Receptors, Retinoic Acid; D025521:Tumor Suppressor Proteins; C082925:retinoic acid receptor beta; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C579096:DAPK1 protein, human; D064550:Death-Associated Protein Kinases; D045643:DNA Repair Enzymes
keywords: Cervical cancer; DNA methylation; MS-HRM
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