Hypermethylated ZNF582 and PAX1 genes in mouth rinse samples as biomarkers for oral dysplasia and oral cancer detection

Shih-Jung Cheng; Chi-Feng Chang; Hui-Hsin Ko; Jang-Jaer Lee; Hsin-Ming Chen; Huei-Jen Wang; Hsiao-Shan Lin; Chun-Pin Chiang

doi:10.1002/hed.24958

Hypermethylated ZNF582 and PAX1 genes in mouth rinse samples as biomarkers for oral dysplasia and oral cancer detection

Head Neck. 2018 Feb;40(2):355-368. doi: 10.1002/hed.24958. Epub 2017 Sep 27.

Authors

Shih-Jung Cheng^{1

2

3}, Chi-Feng Chang^{4

5}, Hui-Hsin Ko^{1

2}, Jang-Jaer Lee^{1

2

3}, Hsin-Ming Chen^{1

2

3}, Huei-Jen Wang⁴, Hsiao-Shan Lin⁴, Chun-Pin Chiang^{1

2

3

6}

Affiliations

¹ Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan.
² Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
³ Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan.
⁴ iStat Biomedical Co, Ltd, New Taipei City, Taiwan.
⁵ Academia-Industry Bridging Program (AIBP), National Research Program for Bio-pharmaceuticals, Taipei, Taiwan.
⁶ Department of Dentistry, Far Eastern Memorial Hospital, New Taipei City, Taiwan.

PMID: 28960639
DOI: 10.1002/hed.24958

Abstract

Background: Effective biomarkers for oral cancer screening are important for early diagnosis and treatment of oral cancer.

Methods: Oral epithelial cell samples collected by mouth rinse were obtained from 65 normal control subjects, 108 patients with oral potentially malignant disorders, and 94 patients with oral squamous cell carcinoma (OSCC). Methylation levels of zinc-finger protein 582 (ZNF582) and paired-box 1 (PAX1) genes were quantified by real-time methylation-specific polymerase chain reaction after bisulfite conversion.

Results: An abrupt increase in methylated ZNF582 (ZNF582^m ) and PAX1 (PAX1^m ) levels and positive rates from mild dysplasia to moderate/severe dysplasia, indicating that both ZNF582^m and PAX1^m are effective biomarkers for differentiating moderate dysplasia or worse (MODY+) oral lesions. When ZNF582^m /PAX1^m tests were used for identifying MODY+ oral lesions, the sensitivity, specificity, and odds ratio (OR) were 0.65/0.64, 0.75/0.82, and 5.6/8.0, respectively.

Conclusion: Hypermethylated ZNF582 and PAX1 genes in oral epithelial cells collected by mouth rinse are effective biomarkers for the detection of oral dysplasia and oral cancer.

Keywords: DNA methylation biomarker; PAX1; ZNF582; mouth rinse; oral cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Biomarkers / analysis
Biomarkers, Tumor / analysis
Biomarkers, Tumor / genetics
Carcinoma, Squamous Cell / diagnosis
Carcinoma, Squamous Cell / genetics*
DNA Methylation
Female
Humans
Kruppel-Like Transcription Factors / analysis
Kruppel-Like Transcription Factors / genetics*
Leukoplakia, Oral / diagnosis
Leukoplakia, Oral / genetics
Male
Middle Aged
Mouth / pathology*
Mouth Neoplasms / diagnosis
Mouth Neoplasms / genetics*
Paired Box Transcription Factors / analysis
Paired Box Transcription Factors / genetics*
Precancerous Conditions / diagnosis
Precancerous Conditions / genetics

Substances

Biomarkers
Biomarkers, Tumor
Kruppel-Like Transcription Factors
Paired Box Transcription Factors
ZNF582 protein, human
PAX1 transcription factor