Hypermethylated ZNF582 and PAX1 are effective biomarkers for detection of oral dysplasia and oral cancer. (November 2016)

• Record Type: Journal Article
• Authors: Cheng, Shih-Jung; Chang, Chi-Feng; Lee, Jang-Jaer; Chen, Hsin-Ming; Wang, Huei-Jen; Liou, Yu-ligh; Yen, Carolyn; Chiang, Chun-Pin
• Is Part Of: Oral oncology. Volume 62(2016:Nov.)
• Page Start: 34
• Page End: 43
• Publication Date: 2016-11
• Subjects: ZNF582 -- PAX1 -- DNA methylation biomarker -- Oral cancer -- Oral dysplasia; Mouth -- Cancer -- Periodicals; Mouth -- Tumors -- Periodicals; Mouth Diseases -- Periodicals; Mouth Neoplasms -- Periodicals; Bouche -- Cancer -- Périodiques; Bouche -- Tumeurs -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9943105
• DOI: 10.1016/j.oraloncology.2016.09.007
• Languages: English
• ISSNs: 1368-8375

Abstract

Highlights: ZNF582 and PAX1 gene methylation levels increased in oral dysplasia and oral cancer. The methylation levels of ZNF582 m and PAX1 m increased in subjects with high-risk oral habits. Hypermethylated ZNF582 and PAX1 are biomarkers for oral dysplasia and oral cancer detection. Hypermethylated ZNF582 and PAX1 are potential biomarkers for oral cancer recurrence detection. Abstract: Objectives: This study investigated whether the methylation of ZNF582, PAX1, SOX1, NKX6.1, and PTPRR genes in oral scrapings could be used to detect oral dysplasia and oral cancer and to predict oral cancer recurrence. Materials and methods: Oral scrapings were collected from 65 normal oral mucosa subjects, 107 oral precancer patients, and 95 oral squamous cell carcinoma patients. Methylation levels of the five genes were quantified by real-time methylation-specific PCR after bisulfite conversion. Results: Among the five tested genes, methylated ZNF582 ( ZNF582 m ) and PAX1 ( PAX1 m ) were found to be appropriate biomarkers for oral dysplasia and oral cancers. ZNF582 m could detect mild dysplasia or worse oral lesions with the sensitivity and specificity being 0.85 and 0.87, respectively. PAX1 m performed better in identifying moderate dysplasia or worse oral lesions with the sensitivity and specificity being 0.72 and 0.86, respectively. Moreover, the methylation levels and positive rates for ZNF582 m and PAX1 m were increased when disease severity increased. Thus, they may be applicable as a triage tool for patients with abnormal visual oral examinations. After cancer excision, both ZNF582 m and PAX1 m levels decreased. However, their levels increased again at the subsequently recurrent sites in some patients approximately 3–4 months before cancer recurrence. Finally, areca-quid chewing alone and in combination with cigarette smoking or alcohol drinking were found to be correlated with ZNF582 and PAX1 hypermethylation. Conclusion: We conclude that hypermethylated ZNF582 and PAX1 are effective biomarkers for the detection of oral dysplasia and oral cancer and for the prediction of oral cancer recurrence.