EDNRB and DCC salivary rinse hypermethylation has a similar performance as expert clinical examination in discrimination of oral cancer/dysplasia versus benign lesions

Juliana Schussel, Xian Chong Zhou, Zhe Zhang, Kavita Pattani, Francisco Bermudez, Germain Jean-Charles, Thomas McCaffrey, Tapan Padhya, Joan Phelan, Silvia Spivakovsky, Mariana Brait, Ryan Li, Helen Yoo Bowne, Judith D. Goldberg, Linda Rolnitzky, Miriam Robbins, A. Ross Kerr, David Sirois, Joseph A. Califano

Research output: Contribution to journalArticle

Abstract

Purpose: Promoter hypermethylation has been recently proposed as a means for head and neck squamous cell carcinoma (HNSCC) detection in salivary rinses. In a prospective study of a high-risk population, we showed that endothelin receptor type B (EDNRB) promoter methylation in salivary rinses is a useful biomarker for oral cancer and premalignancy. Experimental Design: Using that cohort, we evaluated EDNRB methylation status and 8 additional genes. Clinical risk assessment by expert clinicians was conducted and compared with biomarker performance in the prediction of premalignant and malignant disease. Methylation status of 9 genes was analyzed in salivary rinses of 191 patients by quantitative methylation-specific PCR. Results: HOXA9, EDNRB, and deleted in colorectal cancer (DCC) methylation were associated (P = 0.012; P < 0.0001; P = 0.0005) with premalignant or malignant disease. On multivariable modeling, histological diagnosis was only independently associated with EDNRB (P = 0.0003) or DCC (P = 0.004) methylation. A subset of patients received clinical risk classification (CRC) by expert clinicians based on lesion examination. CRC, DCC, and EDNRB were associated with diagnosis of dysplasia/cancer on univariate (P = 0.008; P = 0.026; P = 0.046) and multivariate analysis (P = 0.012; P = 0.037; P = 0.047). CRC identified dysplasia/cancer with 56% of sensitivity and 66% of specificity with a similar area under curve [AUC; 0.61, 95% confidence interval (CI) = 0.60-0.81] when compared to EDNRB and DCC combined AUC (0.60, 95%CI = 0.51-0.69), sensitivity of 46% and specificity of 72%. A combination of EDNRB, DCC, and CRC was optimal AUC (0.67, 95% CI = 0.58-0.76). Conclusions: EDNRB and/or DCC methylation in salivary rinses compares well to examination by an expert clinician in CRC of oral lesions. These salivary biomarkers may be particularly useful in oral premalignancy and malignancy screening in clinical care settings in which expert clinicians are not available.

Original languageEnglish (US)
Pages (from-to)3268-3275
Number of pages8
JournalClinical Cancer Research
Volume19
Issue number12
DOIs
StatePublished - Jun 15 2013

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Endothelin B Receptors
Mouth Neoplasms
Colorectal Neoplasms
Methylation
Area Under Curve
Biomarkers
Confidence Intervals
Endothelin A Receptors
Sensitivity and Specificity
Neoplasms
Genes
Research Design
Multivariate Analysis
Prospective Studies
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

EDNRB and DCC salivary rinse hypermethylation has a similar performance as expert clinical examination in discrimination of oral cancer/dysplasia versus benign lesions. / Schussel, Juliana; Zhou, Xian Chong; Zhang, Zhe; Pattani, Kavita; Bermudez, Francisco; Jean-Charles, Germain; McCaffrey, Thomas; Padhya, Tapan; Phelan, Joan; Spivakovsky, Silvia; Brait, Mariana; Li, Ryan; Bowne, Helen Yoo; Goldberg, Judith D.; Rolnitzky, Linda; Robbins, Miriam; Kerr, A. Ross; Sirois, David; Califano, Joseph A.

In: Clinical Cancer Research, Vol. 19, No. 12, 15.06.2013, p. 3268-3275.

Research output: Contribution to journalArticle

Schussel, J, Zhou, XC, Zhang, Z, Pattani, K, Bermudez, F, Jean-Charles, G, McCaffrey, T, Padhya, T, Phelan, J, Spivakovsky, S, Brait, M, Li, R, Bowne, HY, Goldberg, JD, Rolnitzky, L, Robbins, M, Kerr, AR, Sirois, D & Califano, JA 2013, 'EDNRB and DCC salivary rinse hypermethylation has a similar performance as expert clinical examination in discrimination of oral cancer/dysplasia versus benign lesions', Clinical Cancer Research, vol. 19, no. 12, pp. 3268-3275. https://doi.org/10.1158/1078-0432.CCR-12-3496
Schussel, Juliana ; Zhou, Xian Chong ; Zhang, Zhe ; Pattani, Kavita ; Bermudez, Francisco ; Jean-Charles, Germain ; McCaffrey, Thomas ; Padhya, Tapan ; Phelan, Joan ; Spivakovsky, Silvia ; Brait, Mariana ; Li, Ryan ; Bowne, Helen Yoo ; Goldberg, Judith D. ; Rolnitzky, Linda ; Robbins, Miriam ; Kerr, A. Ross ; Sirois, David ; Califano, Joseph A. / EDNRB and DCC salivary rinse hypermethylation has a similar performance as expert clinical examination in discrimination of oral cancer/dysplasia versus benign lesions. In: Clinical Cancer Research. 2013 ; Vol. 19, No. 12. pp. 3268-3275.
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abstract = "Purpose: Promoter hypermethylation has been recently proposed as a means for head and neck squamous cell carcinoma (HNSCC) detection in salivary rinses. In a prospective study of a high-risk population, we showed that endothelin receptor type B (EDNRB) promoter methylation in salivary rinses is a useful biomarker for oral cancer and premalignancy. Experimental Design: Using that cohort, we evaluated EDNRB methylation status and 8 additional genes. Clinical risk assessment by expert clinicians was conducted and compared with biomarker performance in the prediction of premalignant and malignant disease. Methylation status of 9 genes was analyzed in salivary rinses of 191 patients by quantitative methylation-specific PCR. Results: HOXA9, EDNRB, and deleted in colorectal cancer (DCC) methylation were associated (P = 0.012; P < 0.0001; P = 0.0005) with premalignant or malignant disease. On multivariable modeling, histological diagnosis was only independently associated with EDNRB (P = 0.0003) or DCC (P = 0.004) methylation. A subset of patients received clinical risk classification (CRC) by expert clinicians based on lesion examination. CRC, DCC, and EDNRB were associated with diagnosis of dysplasia/cancer on univariate (P = 0.008; P = 0.026; P = 0.046) and multivariate analysis (P = 0.012; P = 0.037; P = 0.047). CRC identified dysplasia/cancer with 56{\%} of sensitivity and 66{\%} of specificity with a similar area under curve [AUC; 0.61, 95{\%} confidence interval (CI) = 0.60-0.81] when compared to EDNRB and DCC combined AUC (0.60, 95{\%}CI = 0.51-0.69), sensitivity of 46{\%} and specificity of 72{\%}. A combination of EDNRB, DCC, and CRC was optimal AUC (0.67, 95{\%} CI = 0.58-0.76). Conclusions: EDNRB and/or DCC methylation in salivary rinses compares well to examination by an expert clinician in CRC of oral lesions. These salivary biomarkers may be particularly useful in oral premalignancy and malignancy screening in clinical care settings in which expert clinicians are not available.",
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TY - JOUR

T1 - EDNRB and DCC salivary rinse hypermethylation has a similar performance as expert clinical examination in discrimination of oral cancer/dysplasia versus benign lesions

AU - Schussel, Juliana

AU - Zhou, Xian Chong

AU - Zhang, Zhe

AU - Pattani, Kavita

AU - Bermudez, Francisco

AU - Jean-Charles, Germain

AU - McCaffrey, Thomas

AU - Padhya, Tapan

AU - Phelan, Joan

AU - Spivakovsky, Silvia

AU - Brait, Mariana

AU - Li, Ryan

AU - Bowne, Helen Yoo

AU - Goldberg, Judith D.

AU - Rolnitzky, Linda

AU - Robbins, Miriam

AU - Kerr, A. Ross

AU - Sirois, David

AU - Califano, Joseph A.

PY - 2013/6/15

Y1 - 2013/6/15

N2 - Purpose: Promoter hypermethylation has been recently proposed as a means for head and neck squamous cell carcinoma (HNSCC) detection in salivary rinses. In a prospective study of a high-risk population, we showed that endothelin receptor type B (EDNRB) promoter methylation in salivary rinses is a useful biomarker for oral cancer and premalignancy. Experimental Design: Using that cohort, we evaluated EDNRB methylation status and 8 additional genes. Clinical risk assessment by expert clinicians was conducted and compared with biomarker performance in the prediction of premalignant and malignant disease. Methylation status of 9 genes was analyzed in salivary rinses of 191 patients by quantitative methylation-specific PCR. Results: HOXA9, EDNRB, and deleted in colorectal cancer (DCC) methylation were associated (P = 0.012; P < 0.0001; P = 0.0005) with premalignant or malignant disease. On multivariable modeling, histological diagnosis was only independently associated with EDNRB (P = 0.0003) or DCC (P = 0.004) methylation. A subset of patients received clinical risk classification (CRC) by expert clinicians based on lesion examination. CRC, DCC, and EDNRB were associated with diagnosis of dysplasia/cancer on univariate (P = 0.008; P = 0.026; P = 0.046) and multivariate analysis (P = 0.012; P = 0.037; P = 0.047). CRC identified dysplasia/cancer with 56% of sensitivity and 66% of specificity with a similar area under curve [AUC; 0.61, 95% confidence interval (CI) = 0.60-0.81] when compared to EDNRB and DCC combined AUC (0.60, 95%CI = 0.51-0.69), sensitivity of 46% and specificity of 72%. A combination of EDNRB, DCC, and CRC was optimal AUC (0.67, 95% CI = 0.58-0.76). Conclusions: EDNRB and/or DCC methylation in salivary rinses compares well to examination by an expert clinician in CRC of oral lesions. These salivary biomarkers may be particularly useful in oral premalignancy and malignancy screening in clinical care settings in which expert clinicians are not available.

AB - Purpose: Promoter hypermethylation has been recently proposed as a means for head and neck squamous cell carcinoma (HNSCC) detection in salivary rinses. In a prospective study of a high-risk population, we showed that endothelin receptor type B (EDNRB) promoter methylation in salivary rinses is a useful biomarker for oral cancer and premalignancy. Experimental Design: Using that cohort, we evaluated EDNRB methylation status and 8 additional genes. Clinical risk assessment by expert clinicians was conducted and compared with biomarker performance in the prediction of premalignant and malignant disease. Methylation status of 9 genes was analyzed in salivary rinses of 191 patients by quantitative methylation-specific PCR. Results: HOXA9, EDNRB, and deleted in colorectal cancer (DCC) methylation were associated (P = 0.012; P < 0.0001; P = 0.0005) with premalignant or malignant disease. On multivariable modeling, histological diagnosis was only independently associated with EDNRB (P = 0.0003) or DCC (P = 0.004) methylation. A subset of patients received clinical risk classification (CRC) by expert clinicians based on lesion examination. CRC, DCC, and EDNRB were associated with diagnosis of dysplasia/cancer on univariate (P = 0.008; P = 0.026; P = 0.046) and multivariate analysis (P = 0.012; P = 0.037; P = 0.047). CRC identified dysplasia/cancer with 56% of sensitivity and 66% of specificity with a similar area under curve [AUC; 0.61, 95% confidence interval (CI) = 0.60-0.81] when compared to EDNRB and DCC combined AUC (0.60, 95%CI = 0.51-0.69), sensitivity of 46% and specificity of 72%. A combination of EDNRB, DCC, and CRC was optimal AUC (0.67, 95% CI = 0.58-0.76). Conclusions: EDNRB and/or DCC methylation in salivary rinses compares well to examination by an expert clinician in CRC of oral lesions. These salivary biomarkers may be particularly useful in oral premalignancy and malignancy screening in clinical care settings in which expert clinicians are not available.

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