Global methylation silencing of clustered proto-cadherin genes in cervical cancer: Serving as diagnostic markers comparable to HPV

Kai Hung Wang, Cuei Jyuan Lin, Chou Jen Liu, Dai Wei Liu, Rui Lan Huang, Dah Ching Ding, Ching Feng Weng, Tang Yuan Chu

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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 (CIN3) and 20 cervical cancers (CA) versus 12 each of normal, inflammation and CIN1 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 CIN1, 85 CIN2/3, and 38 CA, methylated PCDHA4 and PCDHA13 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 CIN2 or more severe lesion of the cervix, a combination test of methylated PCDHA4 or PCDHA13 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 CIN2 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.

Original languageEnglish
Pages (from-to)43-55
Number of pages13
JournalCancer Medicine
Volume4
Issue number1
DOIs
Publication statusPublished - Jan 1 2015

Fingerprint

Cadherins
Uterine Cervical Neoplasms
Methylation
Cell Adhesion
Genes
Cervical Intraepithelial Neoplasia
Endometrium
Early Detection of Cancer
Epigenomics
Cervix Uteri
Neoplasms
Carcinogenesis
Breast
Neck
Head
Genome
Inflammation
Sensitivity and Specificity
Lung
Liver

Keywords

  • HPV
  • Cancer biomarker
  • Cervical cancer
  • Clustered proto-cadherin
  • DNA methylation

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Global methylation silencing of clustered proto-cadherin genes in cervical cancer : Serving as diagnostic markers comparable to HPV. / Wang, Kai Hung; Lin, Cuei Jyuan; Liu, Chou Jen; Liu, Dai Wei; Huang, Rui Lan; Ding, Dah Ching; Weng, Ching Feng; Chu, Tang Yuan.

In: Cancer Medicine, Vol. 4, No. 1, 01.01.2015, p. 43-55.

Research output: Contribution to journalArticle

Wang, Kai Hung ; Lin, Cuei Jyuan ; Liu, Chou Jen ; Liu, Dai Wei ; Huang, Rui Lan ; Ding, Dah Ching ; Weng, Ching Feng ; Chu, Tang Yuan. / Global methylation silencing of clustered proto-cadherin genes in cervical cancer : Serving as diagnostic markers comparable to HPV. In: Cancer Medicine. 2015 ; Vol. 4, No. 1. pp. 43-55.
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abstract = "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 (CIN3) and 20 cervical cancers (CA) versus 12 each of normal, inflammation and CIN1 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 CIN1, 85 CIN2/3, and 38 CA, methylated PCDHA4 and PCDHA13 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 CIN2 or more severe lesion of the cervix, a combination test of methylated PCDHA4 or PCDHA13 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 CIN2 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.",
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AB - 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 (CIN3) and 20 cervical cancers (CA) versus 12 each of normal, inflammation and CIN1 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 CIN1, 85 CIN2/3, and 38 CA, methylated PCDHA4 and PCDHA13 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 CIN2 or more severe lesion of the cervix, a combination test of methylated PCDHA4 or PCDHA13 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 CIN2 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.

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