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

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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 (PAX1 m) 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 PAX1 m were 87 and 80 % for OSCC detection. The sensitivity of PAX1 m 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.

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Acknowledgments

This study was supported by grant TMU99-AE1-06 from Taipei Medical University; grant no. NSC 100-2314-B-038-042 from the National Science Council, Executive Yuan, Taiwan; and the Teh-Tzer Study Group for Human Medical Research Foundation.

Conflict of interest

The authors received no financial support and declare no potential conflicts of interest with respect to the authorship and/or publication of this article.

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Authors and Affiliations

  1. School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan

    Yung-Kai Huang

  2. Division of Oral and Maxillofacial Surgery, Department of Dentistry, Taipei Medical University Hospital, Taipei, Taiwan

    Bou-Yu Peng & Chia-Yo Wu

  3. School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan

    Bou-Yu Peng & Chia-Yo Wu

  4. School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan

    Chien-Tien Su

  5. Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan

    Chien-Tien Su

  6. Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

    Hui-Chen Wang & Hung-Cheng Lai

  7. Laboratory of Epigenetics and Cancer Stem Cells, National Defense Medical Center, 5F, No. 325, Sec 2, Cheng-Gong Road, Neihu District, Taipei City, 114, Taiwan

    Hung-Cheng Lai

  8. Department and Graduate Institute of Biochemistry, National Defense Medical Center, Taipei, Taiwan

    Hung-Cheng Lai

  9. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Hung-Cheng Lai

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  1. Yung-Kai Huang
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Correspondence to Hung-Cheng Lai.

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Huang, YK., Peng, BY., Wu, CY. et al. DNA methylation of PAX1 as a biomarker for oral squamous cell carcinoma. Clin Oral Invest 18, 801–808 (2014). https://doi.org/10.1007/s00784-013-1048-6

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  • DOI: https://doi.org/10.1007/s00784-013-1048-6

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