Validation of methylation markers for diagnosis of oral cavity cancer

Arantes, Lídia Maria Rebolho Batista; Carvalho, Ana Carolina de; Melendez, Matias Eliseo; Centrone, Cristiane C.; Gois-filho, J.F; Toporcov, Tatiana Natasha; Caly, Décio N.; Tajara, Eloíza H.; Goloni-Bertollo, Eny Maria; Carvalho, André Lopes

doi:10.1016/j.ejca.2015.01.060

Cited by 47 publications

(54 citation statements)

References 37 publications

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“…Ten papers used saliva [9, 10, 12, 14, 17, 27, 29, 32, 50], sixteen papers used solid tissue [11, 15, 16, 18, 19, 23–26, 30, 31, 33–38, 40–46, 49], four papers used blood [21, 28, 31, 39], five papers used both solid tissue and saliva [8, 13, 22, 47, 51], and two papers used both solid tissue and blood (Table 1) [20, 33]. The studies evaluated the diagnostic power of methylation biomarkers as follows: thirty-five studies were based on a single gene [8, 12–14, 16–19, 21, 23, 25–28, 30, 32–51], two papers were based on multiple genes [9, 22] and seven papers were based on both single and multiple genes [10, 11, 15, 20, 24, 29, 31]. The details of methylated biomarkers and their diagnostic powers are shown in Supplementary Table 1.…”

Section: Resultsmentioning

confidence: 99%

Diagnostic accuracy of DNA methylation for head and neck cancer varies by sample type and number of markers tested

Chen

Jiang

et al. 2016

Oncotarget

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Abnormal methylation of certain cancer related genes strongly predicts a diagnosis of head and neck cancer (HNC), while the predictive power of methylation of other DNA markers for HNC remains unclear. To systemically assess the diagnostic value of DNA methylation patterns for HNC and the effect of methylation platform techniques and sample types, we performed a PubMed search for studies of the correlation between DNA methylation and HNC completed before July 2016, and extracted the sensitivity and specificity for methylated biomarkers. Across these studies, DNA methylation showed high sensitivity for diagnosing HNC in solid tissue (0.57), and high specificity in saliva (0.89). Area under the curve (AUC) from summary receiver operating characteristic (SROC) curves revealed that DNA methylation had more diagnostic power in solid tissue (AUC = 0.82) than saliva (AUC = 0.80) or blood (AUC = 0.77). Combinations of multiple methylated genes were more sensitive diagnostic markers than single methylated genes. Our results suggest that the diagnostic accuracy of methylated biomarkers for HNC varied by sample type and were most accurate when results from multiple sample types were considered.

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Section: Resultsmentioning

confidence: 99%

Diagnostic accuracy of DNA methylation for head and neck cancer varies by sample type and number of markers tested

Chen

Jiang

et al. 2016

Oncotarget

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“…DCC is a tumor suppressor gene involved in cell cycle control and apoptosis, and has been implicated in several cancers, including colorectal, esophageal, and ovarian cancer . Interestingly, DCC methylation has been associated with head and neck SCC and in one study, was found to be differentially methylated in head and neck cancer cell lines by HPV status . In a recent study of women undergoing routine cervical cancer screening in Appalachian Ohio, pyrosequencing of candidate genes revealed an association of DCC methylation with increased odds of abnormal cytology .…”

Section: Discussionmentioning

confidence: 99%

Discovery and validation of candidate host DNA methylation markers for detection of cervical precancer and cancer

Clarke

Luhn²,

Gage

et al. 2017

Intl Journal of Cancer

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Human papillomavirus (HPV) testing has been recently introduced as an alternative to cytology for cervical cancer screening. However, since most HPV infections clear without causing clinically relevant lesions, additional triage tests are required to identify women who are at high risk of developing cancer. We performed DNA methylation profiling on formalin-fixed, paraffin-embedded tissue specimens from women with benign HPV16 infection and histologically confirmed cervical intraepithelial neoplasia grade 3, and cancer using a bead-based microarray covering 1,500 CpG sites in over 800 genes. Methylation levels in individual CpG sites were compared using a t-test, and results were summarized by computing p-values. A total of 12 candidate genes (ADCYAP1, ASCL1, ATP10, CADM1, DCC, DBC1, HS3ST2, MOS, MYOD1, SOX1, SOX17 and TMEFF2) identified by DNA methylation profiling, plus an additional three genes identified from the literature (EPB41L3, MAL and miR-124) were chosen for validation in an independent set of 167 liquid-based cytology specimens using pyrosequencing and targeted, next-generation bisulfite sequencing. Of the 15 candidate gene markers, 10 had an area under the curve (AUC) of ≥ 0.75 for discrimination of high grade squamous intraepithelial lesions or worse (HSIL+) from

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“…According to statistics from the Ministry of Health and Welfare, the average survival rate within 5 years after the diagnosis of oral cancer has not improved significantly over the last 20 years [1]. For patients with late-stage OSCC (stages III and IV), the treatments are not very effective, as there is still a high risk of local recurrence and poor survival [2,3]. Therefore, understanding the genetic features of OSCC is needed to help in the control of OSCC.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of Platelet-Derived Growth Factor and Its Receptor Are Correlated with Oral Tumorigenesis and Poor Prognosis in Oral Squamous Cell Carcinoma

Lin

Yang

et al. 2020

IJMS

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Oral squamous cell carcinoma (OSCC) is a cancerous disease with poor prognosis. According to the statistics, the 5-year survival rate has not improved significantly over the past 20 years. The platelet-derived growth factor (PDGF) and its signaling pathway is a key regulator of angiogenesis and tumorigenesis. High level of PDGF and its receptor (PDGFR) have been reported in several types of malignancies. In this study, we investigated the relationship of the molecular expression levels of PDGF and PDGFR with clinicopathological parameters in OSCC. To this end, we measured the mRNA and protein levels of PDGF and PDGFR by real-time quantitative PCR (qRT-PCR), immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA), respectively. We found positive correlations of the mRNA levels of PDGFA, PDGFB, and PDGFRB with lymph node metastasis and poor overall survival (OS). High expression of PDGF, PDGFRA, and PDGFRB were remarkably associated with lymph node metastasis and poor OS, as determined by immunohistochemistry. Preoperative serum levels of PDGF-AA and PDGF-BB had a positive correlation with preoperative platelet count. Elevated serum levels of PDGF-AA. PDGF-BB, and platelet count correlated with lymph node metastasis and an unfavorable outcome. In multivariate Cox regression analysis, PDGFA mRNA, PDGFB mRNA, PDGFRB mRNA, PDGF immunoexpression, PDGFRB immunoexpression, serum PDGF-AA, serum PDGF-BB, and platelet count emerged as significant independent prognostic factors for OS. In vitro, we found that elevated PDGF promotes colony formation, migration, and invasiveness of SAS and OECM-1 cancer cell lines. Our results suggest that the expression level of serum PDGF has the potential to become a useful diagnostic marker for the prognosis of OSCC. In addition, PDGFR should be considered as a potential therapeutic target for OSCC. Furthermore, research should be undertaken to elucidate the role of PDGF and PDGFR regarding the behavior of tumor cells in OSCC.

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Validation of methylation markers for diagnosis of oral cavity cancer

Cited by 47 publications

References 37 publications

Diagnostic accuracy of DNA methylation for head and neck cancer varies by sample type and number of markers tested

Diagnostic accuracy of DNA methylation for head and neck cancer varies by sample type and number of markers tested

Discovery and validation of candidate host DNA methylation markers for detection of cervical precancer and cancer

Overexpression of Platelet-Derived Growth Factor and Its Receptor Are Correlated with Oral Tumorigenesis and Poor Prognosis in Oral Squamous Cell Carcinoma

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