ZNF582 hypermethylation as a prognostic biomarker for malignant transformation of oral lesions

Abstract

Objectives This hospital‐based cohort study evaluated whether ZNF582 and PAX1 methylation levels at baseline can be used as biomarkers to identify lesions with a high potential for malignant transformation in patients with normal mucosa and oral potentially malignant disorders. Patients and methods We recruited 171 adult patients with normal mucosa and oral potentially malignant disorders in 2012–2014. They were followed until 2017. Outcomes, including advanced histopathological findings and oral cancer occurrence, were obtained from medical charts, the Taiwan Cancer Registry, and cause‐of‐death data. Kaplan–Meier analysis and Cox proportional hazards regression models were used to examine the association of ZNF582 and PAX1 methylation levels at baseline with subsequent outcome occurrences. Results After 260,192 days of follow‐up, 11 cases of oral cancer and 4 cases of advanced histopathological progression occurred. Patients with higher ZNF582 and PAX1 methylation levels at baseline had a higher incidence of disease progression. After adjustment for all studied factors using Cox proportional hazards regression models, ZNF582m level (adjusted hazard ratio, 11.41; 95% CI, 2.05–63.36; p = 0.005) was the only significant and independent predictor of disease progression. Conclusions ZNF582 hypermethylation can be an effective and noninvasive biomarker for identifying oral lesions with a high potential for malignant transformation.

A 13-Gene DNA Methylation Analysis Using Oral Brushing Specimens as an Indicator of Oral Cancer Risk: A Descriptive Case Report

“…In two different prospective longitudinal studies, Chang et al and Liu et al showed that p16 methylation was correlated with malignant transformation of OLs with the presence of epithelial dysplasia [ 36 , 37 ]. Juan et al recruited a number of 171 patients with normal oral mucosa and potentially malignant disorders (with or without the presence of dysplasia) and showed that in a follow-up period of 50.6 months, hypermethylation of ZNF582 was the only significant and independent predictor of disease progression [ 38 ]. Finally, two authors analyzed a panel of epigenetic biomarkers with the aim to identify patients surgically treated for OSCC at high risk of secondary neoplastic manifestation.…”

Improving the Diagnostic Performance by Adding Methylation Marker to Conventional Visual Examination in Identifying Oral Cancer

“…Our previous studies have demonstrated that ZNF582 hypermethylation at the adjacent normal oral mucosa in OSCC patients was associated with aggressive progression and poor prognosis [ 29 , 30 ]. Furthermore, a high ZNF582 m level was independently associated with a higher risk of malignant transformation [ 34 ]. Another reason for this observation may originate from the quality and quantity of the sampled specimen, which influenced the results interpreted by the pathologists [ 44 ].…”

“…Among those hypermethylated genes, ZNF582 was studied rigorously and was selected for biomarker development based on promising findings. The correlation between ZNF582 methylation and oral cancer has been extensively studied in recent years [ 29 , 30 , 32 , 33 , 34 , 35 ]. ZNF582 methylation demonstrated as an effective biomarker for the detection of oral dysplasia and oral cancer via collection of oral scrapings from normal oral mucosa subjects, oral potentially malignant patients, and OSCC patients.…”

“…Methylation of ZNF582 may be applicable as a triage tool for patients with abnormal visual oral examinations [ 29 ]. Furthermore, a recent follow-up study has also shown that high incidence of OSCC and oral disease progression was observed in patients with high ZNF582 methylation lesions at baseline [ 34 ].…”

In reply of the comment “Is oral lichen planus potentially malignant: A reply to Yu‐Wei Chiu et al”

“…Among those hypermethylated genes, however, ZNF582 was studied rigorously and continuously in various types of cancers, including oral and cervical cancers, and was selected for biomarker development based on promising findings (Cheng et al, 2018;Cheng et al, 2017;Cheng et al, 2016;Huang et al, 2014;Juan et al, 2021;Li et al, 2019;Sun et al, 2020;van der Zee et al, 2021;van der Zee et al, 2019;Wu et al, 2019;Yang et al, 2018;Zhang et al, 2021;Zhao et al, 2020). Thus, ZNF582 methylation is considered a potential diagnostic aid to the standard practice of visual oral examination for detecting oral cancerous and precancerous lesions (Cheng et al, 2016(Cheng et al, , 2017(Cheng et al, , 2018Juan et al, 2021;Sun et al, 2020;Yang et al, 2018). In a recent follow-up study, a high incidence of OSCC and oral disease progression was observed in patients with high ZNF582 methylation lesions at baseline (Juan et al, 2021).…”