DNA methylation confers clinical potential to predict the oral cancer prognosis

Yang, Cheng Chieh; Wu, Cheng‐Hsien; Chang, Chih-Hung; Hung, Chien-Ping; Sy, Micah; Lin, Hsiao-Shan; Tseng, Chih-Shun

doi:10.15761/crt.1000232

Cited by 5 publications

(6 citation statements)

References 7 publications

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“…Therefore, DNA methylation analysis using buccal smear samples may be used as a molecular screen for oral cancer, particularly in areas with limited resources. A few previous studies investigated interactions between BQ chewing habits and DNA methylation using smear samples from buccal OSCC [8,31]. However, our study is the first report that shows increased levels of DNA methylation in healthy buccal mucosa samples obtained from BQ chewers.…”

Section: Discussionmentioning

confidence: 72%

DNA hypermethylation of sirtuin 1 (SIRT1) caused by betel quid chewing—a possible predictive biomarker for malignant transformation

et al. 2020

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Background: DNA hypermethylation of tumor suppressor genes is observed in precancerous lesions and oral cancer of individuals with the habits of betel quid (BQ) chewing. SIRT1 has been identified as playing a role in the maintenance of epithelial integrity, and its alteration is often related to carcinogenesis. However, the methylation and transcription status of SIRT1 in patients with BQ chewing-related oral cancer has not been investigated. We examined the methylation status of SIRT1 in paraffin-embedded tissue samples of oral squamous cell carcinoma (OSCC) obtained from BQ chewing and non-chewing patients and in tissue samples from healthy control subjects. In addition, we examined whether the hypermethylation of SIRT1 followed by its transcriptional downregulation in the human gingival epithelial cells could be caused by arecoline, a major component of BQ. Furthermore, we investigated the methylation status of SIRT1 in smear samples of macroscopically healthy buccal mucosa from subjects with a habit of BQ chewing. Results: SIRT1 was significantly hypermethylated in tissue samples of OSCC from BQ chewers and non-chewers than in oral mucosa from healthy control subjects. Results also showed that the hypermethylation level of SIRT1 was significantly higher in OSCC of patients with BQ chewing habits than in those of non-chewing habits (p < 0.05). Our in vitro model showed that hypermethylation is followed by downregulation of the transcriptional level of SIRT1 (p < 0.05). The methylation levels of SIRT1 in the smear samples obtained from BQ chewing individuals were significantly higher than those in the samples obtained from individuals that did not chew BQ. The duration of BQ chewing habits was correlated positively to the frequency of SIRT1 hypermethylation (p < 0.05). Conclusions: Our results suggest that DNA hypermethylation of SIRT1 is involved in the occurrence of oral cancer in BQ chewing patients and that hypermethylation in the oral mucosa of BQ chewers could be a predictive marker for the occurrence of malignant transformation. This is the first report that showed DNA hypermethylation in clinically healthy oral epithelium of BQ chewers. Our study shows evidence that DNA hypermethylation may be an early event of oral carcinogenesis prior to observable clinical changes.

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Section: Discussionmentioning

confidence: 72%

DNA hypermethylation of sirtuin 1 (SIRT1) caused by betel quid chewing—a possible predictive biomarker for malignant transformation

et al. 2020

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“…The association between DNA methylation and carcinogenesis has been widely investigated (Asokan et al, 2014; Cheng et al, 2016, 2017, 2018; Kan et al, 2014; Locke et al, 2019; Sharma et al, 2010; Song et al, 2017; Ushijima, 2005; Yang et al, 2018). Several methylated genes have been reported as biomarkers for the detection of precancers, cancers, or disease recurrence or for monitoring therapeutic efficacy, with some of them having been approved as in vitro diagnostic devices (Locke et al, 2019; Song et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

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

Juan¹,

Su²,

Bai

et al. 2021

Oral Diseases

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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.

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“…Previous studies demonstrated that hypermethylation of PAX1 and ZNF582 was associated with OSCC occurrence. Studies using 43 tumor tissues and 42 non‐cancerous matched tissues reported that high methylation levels of both genes in tumors were more commonly observed in poor prognosis patients 13 . However, the correlation between hypermethylation and severity among OSCC patients has not been demonstrated.…”

Section: Discussionmentioning

confidence: 99%

“…Zinc finger protein 582 (ZNF582) , located at chromosome 19q13.43, is a zinc finger protein containing one KRAB‐AB domain and nine zinc finger motifs, 11 which affect cell differentiation, cell proliferation, apoptosis, and neoplastic transformation 12 . PAX1 and ZNF582 hypermethylation was found in oral cancer and cervical cancer 13,14 . In particular, several studies in Taiwan suggested that methylation of PAX1 and ZNF582 is potential biomarkers for OSCC detection 13 .…”

Section: Introductionmentioning

confidence: 99%

“…PAX1 and ZNF582 hypermethylation was found in oral cancer and cervical cancer 13,14 . In particular, several studies in Taiwan suggested that methylation of PAX1 and ZNF582 is potential biomarkers for OSCC detection 13 . Hypermethylation of PAX1 and ZNF582 genes in oral scrapings collected from cancer‐adjacent normal oral mucosal sites was associated with aggressive progression and poor prognosis 15‐17 .…”

Section: Introductionmentioning

confidence: 99%

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Hypermethylated PAX1 and ZNF582 genes in the tissue sample are associated with aggressive progression of oral squamous cell carcinoma

Sun

Juan²,

Su³

et al. 2020

J Oral Pathology Medicine

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Background DNA methylation of paired box gene 1 (PAX1) and zinc finger 582 (ZNF582) is promising cancer biomarkers for oral squamous cell carcinoma detection. This study aims to investigate the correlation between PAX1 or ZNF582 methylation and the progression of oral squamous cell carcinoma (OSCC). Materials and Methods A total of 135 OSCC cases from Peking University School and Hospital of Stomatology were enrolled in this study. Tissue specimens were collected from the lesion site and corresponding adjacent normal site. The methylation level of these two genes was evaluated in primary and recurrent OSCC group. Results Hypermethylation of PAX1 or ZNF582 was observed in lesion sites among primary and recurrent OSCC cases. In the lesion site of primary cases, promoter methylation was observed in T3/T4 (PAX1: P = .02; ZNF582: P = .01), stage III/IV (PAX1: P = .03; ZNF582: P = .01), and bone invasion cases (PAX1: P = .02; ZNF582: P = .047). In the subgroup analysis, the correlation between hypermethylation and OSCC severity remains significant with exposure to smoking/alcohol consumption. Conclusions Hypermethylated PAX1 and ZNF582 can sufficiently act as biomarkers to reflect the severity or progression of OSCC.

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DNA methylation confers clinical potential to predict the oral cancer prognosis

Cited by 5 publications

References 7 publications

DNA hypermethylation of sirtuin 1 (SIRT1) caused by betel quid chewing—a possible predictive biomarker for malignant transformation

DNA hypermethylation of sirtuin 1 (SIRT1) caused by betel quid chewing—a possible predictive biomarker for malignant transformation

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

Hypermethylated PAX1 and ZNF582 genes in the tissue sample are associated with aggressive progression of oral squamous cell carcinoma

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