P16 Methylation as an Early Predictor for Cancer Development From Oral Epithelial Dysplasia: A Double-blind Multicentre Prospective Study
Background: Silencing of P16 through methylation and locus deletion is the most frequent early events in carcinogenesis. The aim of this study is to prospectively determine if early P16 methylation is a predictor for oral cancer development. Methods: Patients (n = 181) with mild or moderate oral epi...
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doaj-977dc37697fd44e498b5cd4c64713a4d2020-11-25T01:24:49ZengElsevierEBioMedicine2352-39642015-05-012543243710.1016/j.ebiom.2015.03.015P16 Methylation as an Early Predictor for Cancer Development From Oral Epithelial Dysplasia: A Double-blind Multicentre Prospective StudyHongwei Liu0Xue-wei Liu1Guangying Dong2Jing Zhou3Yang Liu4Yan Gao5Xiao-yong Liu6Liankun Gu7Zheng Sun8Dajun Deng9Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University School of Stomatology, ChinaCapital Medical University School of Stomatology, ChinaFourth Military Medical University Hospital of Stomatology, ChinaBeijing Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Aetiology, Peking University Cancer Hospital and Institute, ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University School of Stomatology, ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University School of Stomatology, ChinaCapital Medical University School of Stomatology, ChinaBeijing Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Aetiology, Peking University Cancer Hospital and Institute, ChinaCapital Medical University School of Stomatology, ChinaBeijing Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Aetiology, Peking University Cancer Hospital and Institute, ChinaBackground: Silencing of P16 through methylation and locus deletion is the most frequent early events in carcinogenesis. The aim of this study is to prospectively determine if early P16 methylation is a predictor for oral cancer development. Methods: Patients (n = 181) with mild or moderate oral epithelial dysplasia (OED) were recruited into the double blind multicentre cohort. P16 methylation was analyzed using the MethyLight assay. Progression of OEDs was monitored for a minimum 3 year follow-up period. Findings: P16 methylation-informative cases (n = 152) were enrolled in the prospective multicenter cohorts with an ultimate compliance of 96.7%. OED-derived squamous cell carcinomas were observed in 21 patients (14.3%) during the follow-up (median, 41.0 months). The cancer progression rate from the P16 methylation-positive patients was significantly increased when compared to P16 methylation-negative patients [27.1% vs 8.1%; adjusted odds ratio = 4.6; P = 0.006]. When the P16 methylation-positive criteria were used as a biomarker for early prediction of cancer development from OEDs, sensitivity and specificity of 62% and 76% were obtained, respectively. Interpretation: P16 methylation is unequivocally a marker for determining the malignant potential of OED and there is no need for further research regarding this aspect. Funding: National Basic Research Programs of China (2011CB504201 and 2015CB553902), Beijing Science and Technology Commission (Z090507017709016), and Beijing Municipal Administration of Hospital (XM201303) to Dajun Deng. The funding agencies have no role in the actual experimental design, patient recruitment, data collection, analysis, interpretation, or writing of this manuscript.http://www.sciencedirect.com/science/article/pii/S2352396415000821P16MethylationOral dysplasiaTransformationProspective cohort |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hongwei Liu Xue-wei Liu Guangying Dong Jing Zhou Yang Liu Yan Gao Xiao-yong Liu Liankun Gu Zheng Sun Dajun Deng |
spellingShingle |
Hongwei Liu Xue-wei Liu Guangying Dong Jing Zhou Yang Liu Yan Gao Xiao-yong Liu Liankun Gu Zheng Sun Dajun Deng P16 Methylation as an Early Predictor for Cancer Development From Oral Epithelial Dysplasia: A Double-blind Multicentre Prospective Study EBioMedicine P16 Methylation Oral dysplasia Transformation Prospective cohort |
author_facet |
Hongwei Liu Xue-wei Liu Guangying Dong Jing Zhou Yang Liu Yan Gao Xiao-yong Liu Liankun Gu Zheng Sun Dajun Deng |
author_sort |
Hongwei Liu |
title |
P16 Methylation as an Early Predictor for Cancer Development From Oral Epithelial Dysplasia: A Double-blind Multicentre Prospective Study |
title_short |
P16 Methylation as an Early Predictor for Cancer Development From Oral Epithelial Dysplasia: A Double-blind Multicentre Prospective Study |
title_full |
P16 Methylation as an Early Predictor for Cancer Development From Oral Epithelial Dysplasia: A Double-blind Multicentre Prospective Study |
title_fullStr |
P16 Methylation as an Early Predictor for Cancer Development From Oral Epithelial Dysplasia: A Double-blind Multicentre Prospective Study |
title_full_unstemmed |
P16 Methylation as an Early Predictor for Cancer Development From Oral Epithelial Dysplasia: A Double-blind Multicentre Prospective Study |
title_sort |
p16 methylation as an early predictor for cancer development from oral epithelial dysplasia: a double-blind multicentre prospective study |
publisher |
Elsevier |
series |
EBioMedicine |
issn |
2352-3964 |
publishDate |
2015-05-01 |
description |
Background: Silencing of P16 through methylation and locus deletion is the most frequent early events in carcinogenesis. The aim of this study is to prospectively determine if early P16 methylation is a predictor for oral cancer development.
Methods: Patients (n = 181) with mild or moderate oral epithelial dysplasia (OED) were recruited into the double blind multicentre cohort. P16 methylation was analyzed using the MethyLight assay. Progression of OEDs was monitored for a minimum 3 year follow-up period.
Findings: P16 methylation-informative cases (n = 152) were enrolled in the prospective multicenter cohorts with an ultimate compliance of 96.7%. OED-derived squamous cell carcinomas were observed in 21 patients (14.3%) during the follow-up (median, 41.0 months). The cancer progression rate from the P16 methylation-positive patients was significantly increased when compared to P16 methylation-negative patients [27.1% vs 8.1%; adjusted odds ratio = 4.6; P = 0.006]. When the P16 methylation-positive criteria were used as a biomarker for early prediction of cancer development from OEDs, sensitivity and specificity of 62% and 76% were obtained, respectively.
Interpretation: P16 methylation is unequivocally a marker for determining the malignant potential of OED and there is no need for further research regarding this aspect.
Funding: National Basic Research Programs of China (2011CB504201 and 2015CB553902), Beijing Science and Technology Commission (Z090507017709016), and Beijing Municipal Administration of Hospital (XM201303) to Dajun Deng. The funding agencies have no role in the actual experimental design, patient recruitment, data collection, analysis, interpretation, or writing of this manuscript. |
topic |
P16 Methylation Oral dysplasia Transformation Prospective cohort |
url |
http://www.sciencedirect.com/science/article/pii/S2352396415000821 |
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