Hypermethylated ZNF582 and PAX1 genes in oral scrapings collected from cancer-adjacent normal oral mucosal sites are associated with aggressive progression and poor prognosis of oral cancer
Journal
Oral Oncology
Journal Volume
75
Pages
169-177
Date Issued
2017
Author(s)
Chang, Chi-Feng
Liu, Yi-Ching
Peng, Hsin-Hui
Wang, Huei-Jen
Lin, Hsiao-Shan
Abstract
Objective This study assessed whether hypermethylated ZNF582 and PAX1 genes in oral scrapings are correlated with the progression and prognosis of oral squamous cell carcinoma (OSCC). Materials and methods Methylation levels of ZNF582 and PAX1 genes in oral scrapings, collected from the cancer and adjacent normal oral mucosal sites of 80 OSCC patients before surgical cancer excision, were quantified using real-time methylation-specific PCR after bisulfite conversion. Results Both the mean methylation (M)-indices of ZNF582 and PAX1 genes in oral scrapings were significantly higher at the cancer sites than at the adjacent normal oral mucosal sites (both P <.001). In the oral scrapings collected from the adjacent normal oral mucosal sites, the higher M-index of methylated ZNF582 (ZNF582m) was significantly correlated with a more advanced clinical stage (P =.04). Moreover, the higher M-index of methylated PAX1 (PAX1m) was significantly related to larger tumor size (P =.046). When the 80 OSCC patients were classified based on gene methylation tests, using the oral scrapings collected from the adjacent normal oral mucosal sites, we found a significantly shorter 3-year overall survival in ZNF582m-positive, PAX1m-positive, and ZNF582m/PAX1m-positive OSCC patients than in ZNF582m-negative (P =.02), PAX1m-negative (P =.04), and ZNF582m/PAX1m-negative OSCC patients (P =.02), respectively. Multivariate Cox regression analyses identified ZNF582m and ZNF582m/PAX1m as independent unfavorable prognostic factors. Conclusion Hypermethylated ZNF582 and PAX1 genes in the oral scrapings collected from adjacent normal oral mucosal sites rather than cancer sites are associated with aggressive progression and poor prognosis of OSCC. ? 2017 Elsevier Ltd
SDGs
Other Subjects
bisulfite; kruppel like factor; paired box transcription factor; PAX1 transcription factor; ZNF582 protein, human; adult; aged; Article; cancer growth; cancer localization; cancer prognosis; cancer surgery; cancer survival; DNA methylation; female; gene; human; human cell; major clinical study; male; mouth squamous cell carcinoma; overall survival; pax1 gene; priority journal; real time polymerase chain reaction; risk factor; tumor volume; znf582 gene; disease exacerbation; DNA methylation; genetics; metabolism; middle aged; mouth mucosa; mouth tumor; pathology; prognosis; Disease Progression; DNA Methylation; Female; Humans; Kruppel-Like Transcription Factors; Male; Middle Aged; Mouth Mucosa; Mouth Neoplasms; Paired Box Transcription Factors; Prognosis
Publisher
Elsevier Ltd
Type
journal article