Prognostic significance of tumor-related genes hypermethylation detected in cancer-free surgical margins of oral squamous cell carcinomas

Šupić, Gordana; Kozomara, Ružica; Jović, N; Zeljić, Katarina; Magić, Zvonko

doi:10.1016/j.oraloncology.2011.05.014

Cited by 78 publications

(73 citation statements)

References 34 publications

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“…In some histologically negative margins, tumor-specific methylation of P16 and MGMT genes was detected. The presence of methylation markers including P16, CCNA1, DCC 15 , DAPK, ECAD 16 and TMEFF 17 in margin specimens has been associated with clinical outcomes. However, these papers are based on small retrospective patient cohorts, and do not take into account the tumor methylation status.…”

Section: Introductionmentioning

confidence: 99%

Correlation of gene methylation in surgical margin imprints with locoregional recurrence in head and neck squamous cell carcinoma

Hayashi

Roh

et al. 2015

Cancer

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Background Securing negative surgical margins is a critical goal for head and neck surgery. Local recurrence occurs even in some cases with histologically negative surgical margins. Minimal residual tumor cells may lead to locoregional recurrence despite clear histologic margins reported at the time of resection of head and neck squamous cell carcinoma (HNSCC). In order to identify subclinical residual disease, we analyzed deep margin imprint samples collected on one layer nitrocellulose sheets. Methods Bisulfite treated DNA from 73 eligible cases was amplified by quantitative methylation-specific polymerase chain reaction (QMSP) targeting 6 genes (DCC, EDNRB, HOXA9, KIF1A, NID2, NR2B). QMSP values were dichotomized as positive or negative. Associations between the QMSP status of deep margin samples and clinical outcomes were evaluated. Results Two gene methylation combinations among DCC, EDNRB and HOXA9 were associated with decreased locoregional recurrence-free survival (LRFS), recurrence-free survival (RFS) and overall survival (OS). The methylated gene combination EDNRB and HOXA9 in margin imprints was the most powerful predictor of poor LRFS (HR=3.31, 95% CI=1.30-8.46; P=0.012), independent of standard histological factors. In addition, methylation of EDNRB/HOXA9 showed a trend toward reduced RFS (HR=2.74, 95% CI=0.90-8.33; P=0.075) and OS (HR=5.78, 95% CI=0.75-44.7; P=0.093) by multivariable analysis. Conclusion A panel of gene methylation targets in deep surgical margin imprints provides a potential predictive marker of post-operative locoregional recurrence. Intra-operative use of molecular margin-imprint analysis might assist surgeons to obtain rigorously negative surgical margins and improve the outcome of head and neck surgery.

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Section: Introductionmentioning

confidence: 99%

Correlation of gene methylation in surgical margin imprints with locoregional recurrence in head and neck squamous cell carcinoma

Hayashi

Roh

et al. 2015

Cancer

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“…Chronic inflammation of the oral mucosa is another risk factor that can potentially modify the methylation status of various genes in OSCC tumors [25]. The occurrence of multiple CpG methylation sites in a panel of tumor-related genes in OSCC was found to be highly associated with cancer stage and may also correlate with lymph node metastasis [26].…”

Section: Dna Methylation In Oral Carcinogenesismentioning

confidence: 99%

Natural Compounds: DNA Methyltransferase Inhibitors in Oral Squamous Cell Carcinoma

Jha

Aggarwal

Jha

et al. 2015

Appl Biochem Biotechnol

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Oral squamous cell carcinoma (OSCC) is a multistep process which is modulated by several endogenous and environmental factors. Epigenetic changes have been found to be equally responsible for OSCC as genetic changes. A plethora of genes showing hypermethylation have been discovered in OSCC. Since these changes are reversible, a lot of emphasis is on using the natural compounds for their ability to cause demethylation which could lead to reactivation of the inactivated tumor suppressor genes. This review encompasses the promoter hypermethylation of tumor suppressor genes in OSCC and its possible reversal using natural compounds. In addition, new compounds which could be screened for their demethylating ability have also been proposed.

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“…Detection of aberrant methylation of ECAD, MGMT, DAPK, RARb, FHIT, p16, p15, TIMP3, and APC in saliva samples from patients with oral cancer 14 and of HIN-1 and WIF-1 in oral cancer tissue samples has been reported previously. 22,23 Although the aberrant methylation of TMEFF2 and SPARC has been reported …”

Section: Candidate Genes For Oral Cancer Detectionmentioning

confidence: 99%

Aberrant DNA methylation of tumor‐related genes in oral rinse

Nagata

Hamada

Yamada

et al. 2012

Cancer

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BACKGROUND:The early detection of oral squamous cell carcinoma (OSCC) is important, and a screening test with high sensitivity and specificity is urgently needed. Therefore, in this study, the authors investigated the methylation status of tumor-related genes with the objective of establishing a noninvasive method for the detection of OSCC. METHODS: Oral rinse samples were obtained from 34 patients with OSCC and from 24 healthy individuals (controls). The methylation status of 13 genes was determined by using methylation-specific polymerase chain reaction analysis and was quantified using a microchip electrophoresis system. Promoter methylation in each participant was screened by receiver operating characteristic analysis, and the utility of each gene's methylation status, alone and in combination with other genes, was evaluated as a tool for oral cancer detection. RESULTS: Eight of the 13 genes had significantly higher levels of DNA methylation in samples from patients with OSCC than in controls. The genes E-cadherin (ECAD), transmembrane protein with epidermal growth factor-like and 2 follistatin-like domains 2 (TMEFF2), retinoic acid receptor beta (RARb), and O-6 methylguanine DNA methyltransferase (MGMT) had high sensitivity (>75%) and specificity for the detection of oral cancer. OSCC was detected with 100% sensitivity and 87.5% specificity using a combination of ECAD, TMEFF2, RARb, and MGMT and with 97.1% sensitivity and 91.7% specificity using a combination of ECAD, TMEFF2, and MGMT. CONCLUSIONS: The aberrant methylation of a combination of marker genes present in oral rinse samples was used to detect OSCC with >90% sensitivity and specificity. The detection of methylated marker genes from oral rinse samples has great potential for the noninvasive detection of OSCC.

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Prognostic significance of tumor-related genes hypermethylation detected in cancer-free surgical margins of oral squamous cell carcinomas

Cited by 78 publications

References 34 publications

Correlation of gene methylation in surgical margin imprints with locoregional recurrence in head and neck squamous cell carcinoma

Correlation of gene methylation in surgical margin imprints with locoregional recurrence in head and neck squamous cell carcinoma

Natural Compounds: DNA Methyltransferase Inhibitors in Oral Squamous Cell Carcinoma

Aberrant DNA methylation of tumor‐related genes in oral rinse

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