The association between methylated CDKN2A and cervical carcinogenesis, and its diagnostic value in cervical cancer: a meta-analysis

Jinyun Li,1,2,* Chongchang Zhou,1,* Haojie Zhou,3,* Tianlian Bao,1 Tengjiao Gao,1 Xiangling Jiang,1 Meng Ye1,2 1Department of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, 2Department of Medical Oncology, Affiliated Hospital, Ningbo University, 3Department of Molecular D...

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Main Authors: Li J, Zhou C, Zhou H, Bao T, Gao T, Jiang X, Ye M
Format: Article
Language:English
Published: Dove Medical Press 2016-08-01
Series:Therapeutics and Clinical Risk Management
Subjects:
Online Access:https://www.dovepress.com/the-association-between-methylated-cdkn2a--and-cervical-carcinogenesis-peer-reviewed-article-TCRM
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author Li J
Zhou C
Zhou H
Bao T
Gao T
Jiang X
Ye M
author_facet Li J
Zhou C
Zhou H
Bao T
Gao T
Jiang X
Ye M
author_sort Li J
collection DOAJ
description Jinyun Li,1,2,* Chongchang Zhou,1,* Haojie Zhou,3,* Tianlian Bao,1 Tengjiao Gao,1 Xiangling Jiang,1 Meng Ye1,2 1Department of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, 2Department of Medical Oncology, Affiliated Hospital, Ningbo University, 3Department of Molecular Diagnosis, Ningbo Diagnostic Pathology Center, Ningbo, Zhejiang, People’s Republic of China *These authors are co-first authors of this work Background: Cervical cancer is the second deadliest gynecologic malignancy, characterized by apparently precancerous lesions and cervical intraepithelial neoplasia (CIN), and having a long course from the development of CIN to cervical cancer. Cyclin-dependent kinase inhibitor 2A (CDKN2A) is a well-documented tumor suppressor gene and is commonly methylated in cervical cancer. However, the relationship between methylated CDKN2A and carcinogenesis in cervical cancer is inconsistent, and the diagnostic accuracy of methylated CDKN2A is underinvestigated. In this study, we attempted to quantify the association between CDKN2A methylation and the carcinogenesis of cervical cancer, and its diagnostic power.Methods: We systematically reviewed four electronic databases and identified 26 studies involving 1,490 cervical cancers, 1,291 CINs, and 964 controls. A pooled odds ratio (OR) with corresponding 95% confidence intervals (95% CI) was calculated to evaluate the association between methylated CDKN2A and the carcinogenesis of cervical cancer. Specificity, sensitivity, the area under the receiver operating characteristic curve, and the diagnostic odds ratio were computed to assess the effect of methylated CDKN2A in the diagnosis of cervical cancer.Results: Our results indicated an upward trend in the methylation frequency of CDKN2A in the carcinogenesis of cervical cancer (cancer vs control: OR =23.67, 95% CI =15.54–36.06; cancer vs CIN: OR =2.53, 95% CI =1.79–3.5; CIN vs control: OR =9.68, 95% CI =5.82–16.02). The specificity, sensitivity, area under the receiver operating characteristic curve, and diagnostic odds ratio were 0.99 (95% CI: 0.97–0.99), 0.36 (95% CI: 0.28–0.45), 0.93 (95% CI: 0.91–0.95), and 43 (95% CI: 19–98), respectively.Conclusion: Our findings indicate that abnormal CDKN2A methylation may be strongly correlated with the pathogenesis of cervical cancer. Our results also demonstrate that CDKN2A methylation might serve as an early detector of cervical cancer. These findings require further confirmation. Keywords: p16, methylation, cervical cancer carcinogenesis
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spelling doaj.art-6b699e62770a4617868f91bc6ff40a332022-12-21T19:11:20ZengDove Medical PressTherapeutics and Clinical Risk Management1178-203X2016-08-01Volume 121249126028480The association between methylated CDKN2A and cervical carcinogenesis, and its diagnostic value in cervical cancer: a meta-analysisLi JZhou CZhou HBao TGao TJiang XYe MJinyun Li,1,2,* Chongchang Zhou,1,* Haojie Zhou,3,* Tianlian Bao,1 Tengjiao Gao,1 Xiangling Jiang,1 Meng Ye1,2 1Department of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, 2Department of Medical Oncology, Affiliated Hospital, Ningbo University, 3Department of Molecular Diagnosis, Ningbo Diagnostic Pathology Center, Ningbo, Zhejiang, People’s Republic of China *These authors are co-first authors of this work Background: Cervical cancer is the second deadliest gynecologic malignancy, characterized by apparently precancerous lesions and cervical intraepithelial neoplasia (CIN), and having a long course from the development of CIN to cervical cancer. Cyclin-dependent kinase inhibitor 2A (CDKN2A) is a well-documented tumor suppressor gene and is commonly methylated in cervical cancer. However, the relationship between methylated CDKN2A and carcinogenesis in cervical cancer is inconsistent, and the diagnostic accuracy of methylated CDKN2A is underinvestigated. In this study, we attempted to quantify the association between CDKN2A methylation and the carcinogenesis of cervical cancer, and its diagnostic power.Methods: We systematically reviewed four electronic databases and identified 26 studies involving 1,490 cervical cancers, 1,291 CINs, and 964 controls. A pooled odds ratio (OR) with corresponding 95% confidence intervals (95% CI) was calculated to evaluate the association between methylated CDKN2A and the carcinogenesis of cervical cancer. Specificity, sensitivity, the area under the receiver operating characteristic curve, and the diagnostic odds ratio were computed to assess the effect of methylated CDKN2A in the diagnosis of cervical cancer.Results: Our results indicated an upward trend in the methylation frequency of CDKN2A in the carcinogenesis of cervical cancer (cancer vs control: OR =23.67, 95% CI =15.54–36.06; cancer vs CIN: OR =2.53, 95% CI =1.79–3.5; CIN vs control: OR =9.68, 95% CI =5.82–16.02). The specificity, sensitivity, area under the receiver operating characteristic curve, and diagnostic odds ratio were 0.99 (95% CI: 0.97–0.99), 0.36 (95% CI: 0.28–0.45), 0.93 (95% CI: 0.91–0.95), and 43 (95% CI: 19–98), respectively.Conclusion: Our findings indicate that abnormal CDKN2A methylation may be strongly correlated with the pathogenesis of cervical cancer. Our results also demonstrate that CDKN2A methylation might serve as an early detector of cervical cancer. These findings require further confirmation. Keywords: p16, methylation, cervical cancer carcinogenesishttps://www.dovepress.com/the-association-between-methylated-cdkn2a--and-cervical-carcinogenesis-peer-reviewed-article-TCRMp16methylationcervical cancer carcinogenesis
spellingShingle Li J
Zhou C
Zhou H
Bao T
Gao T
Jiang X
Ye M
The association between methylated CDKN2A and cervical carcinogenesis, and its diagnostic value in cervical cancer: a meta-analysis
Therapeutics and Clinical Risk Management
p16
methylation
cervical cancer carcinogenesis
title The association between methylated CDKN2A and cervical carcinogenesis, and its diagnostic value in cervical cancer: a meta-analysis
title_full The association between methylated CDKN2A and cervical carcinogenesis, and its diagnostic value in cervical cancer: a meta-analysis
title_fullStr The association between methylated CDKN2A and cervical carcinogenesis, and its diagnostic value in cervical cancer: a meta-analysis
title_full_unstemmed The association between methylated CDKN2A and cervical carcinogenesis, and its diagnostic value in cervical cancer: a meta-analysis
title_short The association between methylated CDKN2A and cervical carcinogenesis, and its diagnostic value in cervical cancer: a meta-analysis
title_sort association between methylated cdkn2a and cervical carcinogenesis and its diagnostic value in cervical cancer a meta analysis
topic p16
methylation
cervical cancer carcinogenesis
url https://www.dovepress.com/the-association-between-methylated-cdkn2a--and-cervical-carcinogenesis-peer-reviewed-article-TCRM
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