Abstract

Objectives: DNA methylation has been shown to be a promising cancer biomarker. The aim of this study was to evaluate DNA methylation of three transcription factors, sex-determining region Y-box 1 (SOX1), paired box gene 1 (PAX1), and zinc-finger 582 (ZNF582), in detecting oral squamous cell carcinoma (OSCC). Materials and methods: A case-control study was conducted at Taipei Medical University Hospital in Taiwan with 31 cases of various oral cavity squamous cell carcinomas and 40 controls. Questionnaire data assessing environmental exposure, such as alcohol consumption, cigarette smoking, and betel nut chewing, were obtained from each participant. DNA from oral swabs were analyzed for methylation using quantitative methylation polymerase chain reaction with TaqMan probes. Methylation status was determined using a methylation index. Results: Methylation levels of SOX1, PAX1, and ZNF582 were significantly higher in cancer patients (p = 0.02, p = 0.02, and p = 0.03, respectively). Patients with highly methylated SOX1, PAX1, and ZNF582 had an increased cancer risk with odds ratios (ORs) of 16.50 (95 % CI = 2.85-96.65), 60.57 (95 % CI = 5.85-629.94), and 5.07 (95 % CI = 1.08-23.76), respectively. Area under the curve (AUC) values were 0.85, 0.78, and 0.78 for PAX1, SOX1, and ZNF582, respectively. When stratified based on environmental exposure, the AUC of PAX1 methylation (PAX1m) was 0.94 in environmental exposure-naïve subjects and 0.85 for SOX1 methylation in subjects who chewed betel nut. In general, the sensitivity and specificity of PAX1m were 87 and 80 % for OSCC detection. The sensitivity of PAX1m in subjects who chewed betel nut was 83 %, with a specificity of 75 %. Conclusions: Testing PAX1 DNA methylation using oral swabs is a promising method for oral cancer detection. Combined assessments regarding betel nut consumption and DNA methylation can improve OSCC screening. Clinical relevance: The double E (environmental and epigenetic) assessment is a potential strategy in OSCC screening.

Original languageEnglish
Pages (from-to)801-808
Number of pages8
JournalClinical Oral Investigations
Volume18
Issue number3
DOIs
Publication statusPublished - 2014

Fingerprint

DNA Methylation
Methylation
Squamous Cell Carcinoma
Biomarkers
Areca
Zinc Fingers
Environmental Exposure
Area Under Curve
SOXB1 Transcription Factors
Mouth Neoplasms
Mastication
Tumor Biomarkers
Taiwan
Epigenomics
Alcohol Drinking
Mouth
Case-Control Studies
Neoplasms
Smoking
Odds Ratio

Keywords

  • Betel nut
  • Epigenetic-environmental interaction
  • Oral cancer

ASJC Scopus subject areas

  • Dentistry(all)

Cite this

DNA methylation of PAX1 as a biomarker for oral squamous cell carcinoma. / Huang, Yung Kai; Peng, Bou Yu; Wu, Chia Yo; Su, Chien Tien; Wang, Hui Chen; Lai, Hung Cheng.

In: Clinical Oral Investigations, Vol. 18, No. 3, 2014, p. 801-808.

Research output: Contribution to journalArticle

@article{e3c9d28376f84a369c590156c4a004e4,
title = "DNA methylation of PAX1 as a biomarker for oral squamous cell carcinoma",
abstract = "Objectives: DNA methylation has been shown to be a promising cancer biomarker. The aim of this study was to evaluate DNA methylation of three transcription factors, sex-determining region Y-box 1 (SOX1), paired box gene 1 (PAX1), and zinc-finger 582 (ZNF582), in detecting oral squamous cell carcinoma (OSCC). Materials and methods: A case-control study was conducted at Taipei Medical University Hospital in Taiwan with 31 cases of various oral cavity squamous cell carcinomas and 40 controls. Questionnaire data assessing environmental exposure, such as alcohol consumption, cigarette smoking, and betel nut chewing, were obtained from each participant. DNA from oral swabs were analyzed for methylation using quantitative methylation polymerase chain reaction with TaqMan probes. Methylation status was determined using a methylation index. Results: Methylation levels of SOX1, PAX1, and ZNF582 were significantly higher in cancer patients (p = 0.02, p = 0.02, and p = 0.03, respectively). Patients with highly methylated SOX1, PAX1, and ZNF582 had an increased cancer risk with odds ratios (ORs) of 16.50 (95 {\%} CI = 2.85-96.65), 60.57 (95 {\%} CI = 5.85-629.94), and 5.07 (95 {\%} CI = 1.08-23.76), respectively. Area under the curve (AUC) values were 0.85, 0.78, and 0.78 for PAX1, SOX1, and ZNF582, respectively. When stratified based on environmental exposure, the AUC of PAX1 methylation (PAX1m) was 0.94 in environmental exposure-na{\"i}ve subjects and 0.85 for SOX1 methylation in subjects who chewed betel nut. In general, the sensitivity and specificity of PAX1m were 87 and 80 {\%} for OSCC detection. The sensitivity of PAX1m in subjects who chewed betel nut was 83 {\%}, with a specificity of 75 {\%}. Conclusions: Testing PAX1 DNA methylation using oral swabs is a promising method for oral cancer detection. Combined assessments regarding betel nut consumption and DNA methylation can improve OSCC screening. Clinical relevance: The double E (environmental and epigenetic) assessment is a potential strategy in OSCC screening.",
keywords = "Betel nut, Epigenetic-environmental interaction, Oral cancer",
author = "Huang, {Yung Kai} and Peng, {Bou Yu} and Wu, {Chia Yo} and Su, {Chien Tien} and Wang, {Hui Chen} and Lai, {Hung Cheng}",
year = "2014",
doi = "10.1007/s00784-013-1048-6",
language = "English",
volume = "18",
pages = "801--808",
journal = "Clinical Oral Investigations",
issn = "1432-6981",
publisher = "Springer Verlag",
number = "3",

}

TY - JOUR

T1 - DNA methylation of PAX1 as a biomarker for oral squamous cell carcinoma

AU - Huang, Yung Kai

AU - Peng, Bou Yu

AU - Wu, Chia Yo

AU - Su, Chien Tien

AU - Wang, Hui Chen

AU - Lai, Hung Cheng

PY - 2014

Y1 - 2014

N2 - Objectives: DNA methylation has been shown to be a promising cancer biomarker. The aim of this study was to evaluate DNA methylation of three transcription factors, sex-determining region Y-box 1 (SOX1), paired box gene 1 (PAX1), and zinc-finger 582 (ZNF582), in detecting oral squamous cell carcinoma (OSCC). Materials and methods: A case-control study was conducted at Taipei Medical University Hospital in Taiwan with 31 cases of various oral cavity squamous cell carcinomas and 40 controls. Questionnaire data assessing environmental exposure, such as alcohol consumption, cigarette smoking, and betel nut chewing, were obtained from each participant. DNA from oral swabs were analyzed for methylation using quantitative methylation polymerase chain reaction with TaqMan probes. Methylation status was determined using a methylation index. Results: Methylation levels of SOX1, PAX1, and ZNF582 were significantly higher in cancer patients (p = 0.02, p = 0.02, and p = 0.03, respectively). Patients with highly methylated SOX1, PAX1, and ZNF582 had an increased cancer risk with odds ratios (ORs) of 16.50 (95 % CI = 2.85-96.65), 60.57 (95 % CI = 5.85-629.94), and 5.07 (95 % CI = 1.08-23.76), respectively. Area under the curve (AUC) values were 0.85, 0.78, and 0.78 for PAX1, SOX1, and ZNF582, respectively. When stratified based on environmental exposure, the AUC of PAX1 methylation (PAX1m) was 0.94 in environmental exposure-naïve subjects and 0.85 for SOX1 methylation in subjects who chewed betel nut. In general, the sensitivity and specificity of PAX1m were 87 and 80 % for OSCC detection. The sensitivity of PAX1m in subjects who chewed betel nut was 83 %, with a specificity of 75 %. Conclusions: Testing PAX1 DNA methylation using oral swabs is a promising method for oral cancer detection. Combined assessments regarding betel nut consumption and DNA methylation can improve OSCC screening. Clinical relevance: The double E (environmental and epigenetic) assessment is a potential strategy in OSCC screening.

AB - Objectives: DNA methylation has been shown to be a promising cancer biomarker. The aim of this study was to evaluate DNA methylation of three transcription factors, sex-determining region Y-box 1 (SOX1), paired box gene 1 (PAX1), and zinc-finger 582 (ZNF582), in detecting oral squamous cell carcinoma (OSCC). Materials and methods: A case-control study was conducted at Taipei Medical University Hospital in Taiwan with 31 cases of various oral cavity squamous cell carcinomas and 40 controls. Questionnaire data assessing environmental exposure, such as alcohol consumption, cigarette smoking, and betel nut chewing, were obtained from each participant. DNA from oral swabs were analyzed for methylation using quantitative methylation polymerase chain reaction with TaqMan probes. Methylation status was determined using a methylation index. Results: Methylation levels of SOX1, PAX1, and ZNF582 were significantly higher in cancer patients (p = 0.02, p = 0.02, and p = 0.03, respectively). Patients with highly methylated SOX1, PAX1, and ZNF582 had an increased cancer risk with odds ratios (ORs) of 16.50 (95 % CI = 2.85-96.65), 60.57 (95 % CI = 5.85-629.94), and 5.07 (95 % CI = 1.08-23.76), respectively. Area under the curve (AUC) values were 0.85, 0.78, and 0.78 for PAX1, SOX1, and ZNF582, respectively. When stratified based on environmental exposure, the AUC of PAX1 methylation (PAX1m) was 0.94 in environmental exposure-naïve subjects and 0.85 for SOX1 methylation in subjects who chewed betel nut. In general, the sensitivity and specificity of PAX1m were 87 and 80 % for OSCC detection. The sensitivity of PAX1m in subjects who chewed betel nut was 83 %, with a specificity of 75 %. Conclusions: Testing PAX1 DNA methylation using oral swabs is a promising method for oral cancer detection. Combined assessments regarding betel nut consumption and DNA methylation can improve OSCC screening. Clinical relevance: The double E (environmental and epigenetic) assessment is a potential strategy in OSCC screening.

KW - Betel nut

KW - Epigenetic-environmental interaction

KW - Oral cancer

UR - http://www.scopus.com/inward/record.url?scp=84897575758&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84897575758&partnerID=8YFLogxK

U2 - 10.1007/s00784-013-1048-6

DO - 10.1007/s00784-013-1048-6

M3 - Article

C2 - 23907469

AN - SCOPUS:84897575758

VL - 18

SP - 801

EP - 808

JO - Clinical Oral Investigations

JF - Clinical Oral Investigations

SN - 1432-6981

IS - 3

ER -