Salivary Epigenetic Biomarkers in Head and Neck Squamous Cell Carcinomas

Lim, Yenkai; Sun, Charles Xiaohang; Tran, Peter; Punyadeera, Chamindie

doi:10.2217/bmm.16.2

Cited by 25 publications

(15 citation statements)

References 114 publications

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“…Several studies have been carried out to explore the association between changes in DNA methylation and tumor progression of HNSCC. In fact, the DNA hypermethylation of tumor suppressor genes is an earlier event in carcinogenesis, and is responsible for uncontrolled cellular proliferation, which suggests that DNA hypermethylation is a potential marker for early diagnosis of HNSCC [ 89 ].…”

Section: Epigenetic Modifications Associated With Tumor Progressiomentioning

confidence: 99%

Epigenetic Modifications and Head and Neck Cancer: Implications for Tumor Progression and Resistance to Therapy

Castilho

Squarize

Almeida

2017

IJMS

136

121

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Head and neck squamous carcinoma (HNSCC) is the sixth most prevalent cancer and one of the most aggressive malignancies worldwide. Despite continuous efforts to identify molecular markers for early detection, and to develop efficient treatments, the overall survival and prognosis of HNSCC patients remain poor. Accumulated scientific evidences suggest that epigenetic alterations, including DNA methylation, histone covalent modifications, chromatin remodeling and non-coding RNAs, are frequently involved in oral carcinogenesis, tumor progression, and resistance to therapy. Epigenetic alterations occur in an unsystematic manner or as part of the aberrant transcriptional machinery, which promotes selective advantage to the tumor cells. Epigenetic modifications also contribute to cellular plasticity during tumor progression and to the formation of cancer stem cells (CSCs), a small subset of tumor cells with self-renewal ability. CSCs are involved in the development of intrinsic or acquired therapy resistance, and tumor recurrences or relapse. Therefore, the understanding and characterization of epigenetic modifications associated with head and neck carcinogenesis, and the prospective identification of epigenetic markers associated with CSCs, hold the promise for novel therapeutic strategies to fight tumors. In this review, we focus on the current knowledge on epigenetic modifications observed in HNSCC and emerging Epi-drugs capable of sensitizing HNSCC to therapy.

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Section: Epigenetic Modifications Associated With Tumor Progressiomentioning

confidence: 99%

Epigenetic Modifications and Head and Neck Cancer: Implications for Tumor Progression and Resistance to Therapy

Castilho

Squarize

Almeida

2017

IJMS

136

121

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“…Early recognition of the symptoms and signs, as well as prompt diagnosis of OCC and OPC is vital for patient survival. However, due to the lack of early screening/diagnostic tools, these cancer types are often diagnosed at advanced stages, resulting in poor survival outcomes (5-year mortality rate of 40–50%) (Lam et al, 2007 ; Kulasinghe, 2015 ; Lim et al, 2016a ). To improve patient survival, saliva diagnostics have played a central role in the discovery of biomarkers for OCC and OPC early detection.…”

Section: Introductionmentioning

confidence: 99%

The Performance of an Oral Microbiome Biomarker Panel in Predicting Oral Cavity and Oropharyngeal Cancers

Lim

Fukuma

Totsika

et al. 2018

Front. Cell. Infect. Microbiol.

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The oral microbiome can play a role in the instigation and progression of oral diseases that can manifest into other systemic conditions. These associations encourage the exploration of oral dysbiosis leading to the pathogenesis of cancers. In this study, oral rinse was used to characterize the oral microbiome fluctuation associated with oral cavity cancer (OCC) and oropharyngeal cancers (OPC). The study cohort consists of normal healthy controls (n = 10, between 20 and 30 years of age; n = 10, above 50 years of age), high-risk individuals (n = 11, above 50 years of age with bad oral hygiene and/or oral diseases) and OCC and OPC patients (n = 31, HPV-positive; n = 21, HPV-negative). Oral rinse samples were analyzed using 16S rRNA gene amplicon sequencing on the MiSeq platform. Kruskal–Wallis rank test was used to identify genera associated with OCC and OPC. A logistic regression analysis was carried out to determine the performance of these genera as a biomarker panel to predict OCC and OPC. In addition, a two-fold cross-validation with a bootstrap procedure was carried out in R to investigate how well the panel would perform in an emulated clinical scenario. Our data indicate that the oral microbiome is able to predict the presence of OCC and OPC with sensitivity and specificity of 100 and 90%, respectively. With further validation, the panel could potentially be implemented into clinical diagnostic and prognostic workflows for OCC and OPC.

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“…Head and neck squamous cell carcinomas (HNSCCs) encompasses tumours within the oral cavity, pharynx, larynx, paranasal sinuses, nasal cavity and salivary glands, and are some of the most aggressive cancer types [ 1 , 2 ]. Main risk factors for HNSCC include smoking, alcohol consumption, betel quid chewing, and Human Papillomavirus (HPV, mainly HPV-16 and HPV-18) infections [ 2 – 4 ]. HPV-positive and HPV-negative cancers are biologically and clinically different and as such require different treatment and clinical management [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Salivary DNA methylation panel to diagnose HPV-positive and HPV-negative head and neck cancers

et al. 2016

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BackgroundHead and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of tumours with a typical 5 year survival rate of <40 %. DNA methylation in tumour-suppressor genes often occurs at an early stage of tumorigenesis, hence DNA methylation can be used as an early tumour biomarker. Saliva is an ideal diagnostic medium to detect early HNSCC tumour activities due to its proximity to tumour site, non-invasiveness and ease of sampling. We test the hypothesis that the surveillance of DNA methylation in five tumour-suppressor genes (RASSF1α, p16 INK4a, TIMP3, PCQAP/MED15) will allow us to diagnose HNSCC patients from a normal healthy control group as well as to discriminate between Human Papillomavirus (HPV)-positive and HPV-negative patients.MethodsMethylation-specific PCR (MSP) was used to determine the methylation levels of RASSF1α, p16 INK4a, TIMP3 and PCQAP/MED15 in DNA isolated from saliva. Statistical analysis was carried out using non-parametric Mann-Whitney’s U-test for individually methylated genes. A logistic regression analysis was carried out to determine the assay sensitivity when combing the five genes. Further, a five-fold cross-validation with a bootstrap procedure was carried out to determine how well the panel will perform in a real clinical scenario.ResultsSalivary DNA methylation levels were not affected by age. Salivary DNA methylation levels for RASSF1α, p16 INK4a, TIMP3 and PCQAP/MED15 were higher in HPV-negative HNSCC patients (n = 88) compared with a normal healthy control group (n = 122) (sensitivity of 71 % and specificity of 80 %). Conversely, DNA methylation levels for these genes were lower in HPV-positive HNSCC patients (n = 45) compared with a normal healthy control group (sensitivity of 80 % and specificity of 74 %), consistent with the proposed aetiology of HPV-positive HNSCCs.ConclusionsSalivary DNA tumour-suppressor methylation gene panel has the potential to detect early-stage tumours in HPV-negative HNSCC patients. HPV infection was found to deregulate the methylation levels in HPV-positive HNSCC patients. Large-scale double-blinded clinical trials are crucial before this panel can potentially be integrated into a clinical setting.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2785-0) contains supplementary material, which is available to authorized users.

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Salivary Epigenetic Biomarkers in Head and Neck Squamous Cell Carcinomas

Cited by 25 publications

References 114 publications

Epigenetic Modifications and Head and Neck Cancer: Implications for Tumor Progression and Resistance to Therapy

Epigenetic Modifications and Head and Neck Cancer: Implications for Tumor Progression and Resistance to Therapy

The Performance of an Oral Microbiome Biomarker Panel in Predicting Oral Cavity and Oropharyngeal Cancers

Salivary DNA methylation panel to diagnose HPV-positive and HPV-negative head and neck cancers

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