Open AccessGlobal methylation silencing of clustered proto‐cadherin genes in cervical cancer: serving as diagnostic markers comparable to HPV
Author(s) -
Wang KaiHung,
Lin CueiJyuan,
Liu ChouJen,
Liu DaiWei,
Huang RuiLan,
Ding DahChing,
Weng ChingFeng,
Chu TangYuan
Publication year - 2015
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.335
Subject(s) - methylation , cervical intraepithelial neoplasia , cervix , dna methylation , carcinogenesis , cervical cancer , cancer , gene silencing , epigenetics , medicine , cancer research , pathology , oncology , gastroenterology , gene , biology , genetics , gene expression
Epigenetic remodeling of cell adhesion genes is a common phenomenon in cancer invasion. This study aims to investigate global methylation of cell adhesion genes in cervical carcinogenesis and to apply them in early detection of cancer from cervical scraping. Genome‐wide methylation array was performed on an investigation cohort, including 16 cervical intraepithelial neoplasia 3 ( CIN 3) and 20 cervical cancers ( CA ) versus 12 each of normal, inflammation and CIN 1 as controls. Twelve members of clustered proto‐cadherin ( PCDH ) genes were collectively methylated and silenced, which were validated in cancer cells of the cervix, endometrium, liver, head and neck, breast, and lung. In an independent cohort including 107 controls, 66 CIN 1, 85 CIN 2/3, and 38 CA , methylated PCDHA 4 and PCDHA 13 were detected in 2.8%, 24.2%, 52.9%, and 84.2% ( P < 10 −25 ), and 2.8%, 24.2%, 50.6%, and 94.7% ( P < 10 −29 ), respectively. In diagnosis of CIN 2 or more severe lesion of the cervix, a combination test of methylated PCDHA 4 or PCDHA 13 from cervical scraping had a sensitivity, specificity, positive predictive value, and negative predictive value of 74.8%, 80.3%, 73%, and 81.8%, respectively. Testing of this combination from cervical scraping is equally sensitive but more specific than human papillomavirus ( HPV ) test in diagnosis of CIN 2 or more severe lesions. The study disclosed a collective methylation of PCDH genes in cancer of cervix and other sites. At least two of them can be promising diagnostic markers for cervical cancer noninferior to HPV .