A similar effect of P16 hydroxymethylation and true-methylation on the prediction of malignant transformation of oral epithelial dysplasia: Observation from a prospective study 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis

Hongwei Liu, Zhaojun Liu, Xue Wei Liu, Si Xu, Lei Wang, Yang Liu, Jing Zhou, Liankun Gu, Yan Gao, Xiao Yong Liu, Huidong Shi, Zheng Sun, Dajun Deng

Research output: Contribution to journalArticle

Abstract

Background: Total P16 methylation (P16M), including P16 hydroxymethylation (P16H) and true-P16M, correlates with malignant transformation of oral epithelial dysplasia (OED). Both true-P16M and P16H are early events in carcinogenesis. The aim of this study is to prospectively determine if discrimination of true-P16M from P16H is necessary for prediction of cancer development from OEDs. Methods: Patients (n = 265) with mild or moderate OED were recruited into the double blind two-center cohort. Total-P16M and P16H were analyzed using the 115-bp MethyLight, TET-assisted bisulfite (TAB) methylation-specific PCR (MSP), and TAB-sequencing. Total-P16M-positive and P16H-negative samples were defined as true-P16M-positive. Progression of OEDs was monitored for a minimum 24 months follow-up period. Results: P16H was detected in 23 of 73 (31.5%) total-P16M-positive OEDs. Follow-up information was obtained from 247 patients with an ultimate compliance rate of 93.2%. OED-derived squamous cell carcinomas were observed in 13.0% (32/247) patients during follow-up (median, 41.0 months). The cancer progression rate for total-P16M-positive patients was significantly increased when compared to total-P16M-negative patients [23.3% vs 8.6%; adjusted odds ratio = 2.67 (95% CI: 1.19-5.99)]. However, the cancer progression rates were similar between P16H- and true-P16M-positive OEDs [26.1% (6/23) vs 22.0% (11/50); odds ratio = 0.80 (95% CI: 0.22-2.92)]. The cancer-free survival was also similar for these patients. Conclusion: P16H and true-P16M are similar biomarkers for determining malignant potential of OEDs. Discrimination of P16H from true-P16M, at least in OED, may be not necessary in clinical applications. Trial registration: This study is registered prospectively in the U.S. National Institutes of Health Clinical Trials Protocol Registration System (trial number NCT02967120, available at https://ClinicalTrials.gov/ct2/show/NCT02967120).

Original languageEnglish (US)
Article number918
JournalBMC Cancer
Volume18
Issue number1
DOIs
StatePublished - Sep 24 2018

Fingerprint

Methylation
Carcinogenesis
Observation
Prospective Studies
Health
Clinical Protocols
Neoplasms
Odds Ratio
National Institutes of Health (U.S.)
Squamous Cell Carcinoma
Biomarkers
Clinical Trials

Keywords

  • Hydroxymethylation
  • Malignant transformation
  • Oral epithelial dysplasia
  • P16
  • Prospective cohort

ASJC Scopus subject areas

  • Genetics
  • Oncology
  • Cancer Research

Cite this

A similar effect of P16 hydroxymethylation and true-methylation on the prediction of malignant transformation of oral epithelial dysplasia : Observation from a prospective study 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis. / Liu, Hongwei; Liu, Zhaojun; Liu, Xue Wei; Xu, Si; Wang, Lei; Liu, Yang; Zhou, Jing; Gu, Liankun; Gao, Yan; Liu, Xiao Yong; Shi, Huidong; Sun, Zheng; Deng, Dajun.

In: BMC Cancer, Vol. 18, No. 1, 918, 24.09.2018.

Research output: Contribution to journalArticle

Liu, Hongwei ; Liu, Zhaojun ; Liu, Xue Wei ; Xu, Si ; Wang, Lei ; Liu, Yang ; Zhou, Jing ; Gu, Liankun ; Gao, Yan ; Liu, Xiao Yong ; Shi, Huidong ; Sun, Zheng ; Deng, Dajun. / A similar effect of P16 hydroxymethylation and true-methylation on the prediction of malignant transformation of oral epithelial dysplasia : Observation from a prospective study 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis. In: BMC Cancer. 2018 ; Vol. 18, No. 1.
@article{6e06a4743b8c4568873a3daabed18ca5,
title = "A similar effect of P16 hydroxymethylation and true-methylation on the prediction of malignant transformation of oral epithelial dysplasia: Observation from a prospective study 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis",
abstract = "Background: Total P16 methylation (P16M), including P16 hydroxymethylation (P16H) and true-P16M, correlates with malignant transformation of oral epithelial dysplasia (OED). Both true-P16M and P16H are early events in carcinogenesis. The aim of this study is to prospectively determine if discrimination of true-P16M from P16H is necessary for prediction of cancer development from OEDs. Methods: Patients (n = 265) with mild or moderate OED were recruited into the double blind two-center cohort. Total-P16M and P16H were analyzed using the 115-bp MethyLight, TET-assisted bisulfite (TAB) methylation-specific PCR (MSP), and TAB-sequencing. Total-P16M-positive and P16H-negative samples were defined as true-P16M-positive. Progression of OEDs was monitored for a minimum 24 months follow-up period. Results: P16H was detected in 23 of 73 (31.5{\%}) total-P16M-positive OEDs. Follow-up information was obtained from 247 patients with an ultimate compliance rate of 93.2{\%}. OED-derived squamous cell carcinomas were observed in 13.0{\%} (32/247) patients during follow-up (median, 41.0 months). The cancer progression rate for total-P16M-positive patients was significantly increased when compared to total-P16M-negative patients [23.3{\%} vs 8.6{\%}; adjusted odds ratio = 2.67 (95{\%} CI: 1.19-5.99)]. However, the cancer progression rates were similar between P16H- and true-P16M-positive OEDs [26.1{\%} (6/23) vs 22.0{\%} (11/50); odds ratio = 0.80 (95{\%} CI: 0.22-2.92)]. The cancer-free survival was also similar for these patients. Conclusion: P16H and true-P16M are similar biomarkers for determining malignant potential of OEDs. Discrimination of P16H from true-P16M, at least in OED, may be not necessary in clinical applications. Trial registration: This study is registered prospectively in the U.S. National Institutes of Health Clinical Trials Protocol Registration System (trial number NCT02967120, available at https://ClinicalTrials.gov/ct2/show/NCT02967120).",
keywords = "Hydroxymethylation, Malignant transformation, Oral epithelial dysplasia, P16, Prospective cohort",
author = "Hongwei Liu and Zhaojun Liu and Liu, {Xue Wei} and Si Xu and Lei Wang and Yang Liu and Jing Zhou and Liankun Gu and Yan Gao and Liu, {Xiao Yong} and Huidong Shi and Zheng Sun and Dajun Deng",
year = "2018",
month = "9",
day = "24",
doi = "10.1186/s12885-018-4787-6",
language = "English (US)",
volume = "18",
journal = "BMC Cancer",
issn = "1471-2407",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - A similar effect of P16 hydroxymethylation and true-methylation on the prediction of malignant transformation of oral epithelial dysplasia

T2 - Observation from a prospective study 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis

AU - Liu, Hongwei

AU - Liu, Zhaojun

AU - Liu, Xue Wei

AU - Xu, Si

AU - Wang, Lei

AU - Liu, Yang

AU - Zhou, Jing

AU - Gu, Liankun

AU - Gao, Yan

AU - Liu, Xiao Yong

AU - Shi, Huidong

AU - Sun, Zheng

AU - Deng, Dajun

PY - 2018/9/24

Y1 - 2018/9/24

N2 - Background: Total P16 methylation (P16M), including P16 hydroxymethylation (P16H) and true-P16M, correlates with malignant transformation of oral epithelial dysplasia (OED). Both true-P16M and P16H are early events in carcinogenesis. The aim of this study is to prospectively determine if discrimination of true-P16M from P16H is necessary for prediction of cancer development from OEDs. Methods: Patients (n = 265) with mild or moderate OED were recruited into the double blind two-center cohort. Total-P16M and P16H were analyzed using the 115-bp MethyLight, TET-assisted bisulfite (TAB) methylation-specific PCR (MSP), and TAB-sequencing. Total-P16M-positive and P16H-negative samples were defined as true-P16M-positive. Progression of OEDs was monitored for a minimum 24 months follow-up period. Results: P16H was detected in 23 of 73 (31.5%) total-P16M-positive OEDs. Follow-up information was obtained from 247 patients with an ultimate compliance rate of 93.2%. OED-derived squamous cell carcinomas were observed in 13.0% (32/247) patients during follow-up (median, 41.0 months). The cancer progression rate for total-P16M-positive patients was significantly increased when compared to total-P16M-negative patients [23.3% vs 8.6%; adjusted odds ratio = 2.67 (95% CI: 1.19-5.99)]. However, the cancer progression rates were similar between P16H- and true-P16M-positive OEDs [26.1% (6/23) vs 22.0% (11/50); odds ratio = 0.80 (95% CI: 0.22-2.92)]. The cancer-free survival was also similar for these patients. Conclusion: P16H and true-P16M are similar biomarkers for determining malignant potential of OEDs. Discrimination of P16H from true-P16M, at least in OED, may be not necessary in clinical applications. Trial registration: This study is registered prospectively in the U.S. National Institutes of Health Clinical Trials Protocol Registration System (trial number NCT02967120, available at https://ClinicalTrials.gov/ct2/show/NCT02967120).

AB - Background: Total P16 methylation (P16M), including P16 hydroxymethylation (P16H) and true-P16M, correlates with malignant transformation of oral epithelial dysplasia (OED). Both true-P16M and P16H are early events in carcinogenesis. The aim of this study is to prospectively determine if discrimination of true-P16M from P16H is necessary for prediction of cancer development from OEDs. Methods: Patients (n = 265) with mild or moderate OED were recruited into the double blind two-center cohort. Total-P16M and P16H were analyzed using the 115-bp MethyLight, TET-assisted bisulfite (TAB) methylation-specific PCR (MSP), and TAB-sequencing. Total-P16M-positive and P16H-negative samples were defined as true-P16M-positive. Progression of OEDs was monitored for a minimum 24 months follow-up period. Results: P16H was detected in 23 of 73 (31.5%) total-P16M-positive OEDs. Follow-up information was obtained from 247 patients with an ultimate compliance rate of 93.2%. OED-derived squamous cell carcinomas were observed in 13.0% (32/247) patients during follow-up (median, 41.0 months). The cancer progression rate for total-P16M-positive patients was significantly increased when compared to total-P16M-negative patients [23.3% vs 8.6%; adjusted odds ratio = 2.67 (95% CI: 1.19-5.99)]. However, the cancer progression rates were similar between P16H- and true-P16M-positive OEDs [26.1% (6/23) vs 22.0% (11/50); odds ratio = 0.80 (95% CI: 0.22-2.92)]. The cancer-free survival was also similar for these patients. Conclusion: P16H and true-P16M are similar biomarkers for determining malignant potential of OEDs. Discrimination of P16H from true-P16M, at least in OED, may be not necessary in clinical applications. Trial registration: This study is registered prospectively in the U.S. National Institutes of Health Clinical Trials Protocol Registration System (trial number NCT02967120, available at https://ClinicalTrials.gov/ct2/show/NCT02967120).

KW - Hydroxymethylation

KW - Malignant transformation

KW - Oral epithelial dysplasia

KW - P16

KW - Prospective cohort

UR - http://www.scopus.com/inward/record.url?scp=85053853619&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053853619&partnerID=8YFLogxK

U2 - 10.1186/s12885-018-4787-6

DO - 10.1186/s12885-018-4787-6

M3 - Article

C2 - 30249192

AN - SCOPUS:85053853619

VL - 18

JO - BMC Cancer

JF - BMC Cancer

SN - 1471-2407

IS - 1

M1 - 918

ER -