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PMID: 22228635 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Detection of TIMP3 promoter hypermethylation in salivary rinse as an independent predictor of local recurrence-free survival in head and neck cancer.

Clinical cancer research : an official journal of the American Association for Cancer Research ·Vol. 18 ·No. 4 ·2012-02-15 ·Pages 1082-91

Sun W, Zaboli D, Wang H, Liu Y, Arnaoutakis D, Khan T, Khan Z, Koch WM, Califano JA

Abstract

To validate a panel of methylation-based salivary rinse biomarkers (P16, CCNA1, DCC, TIMP3, MGMT, DAPK, and MINT31) previously shown to be independently associated with poor overall survival and local recurrence in a larger, separate cohort of patients with head and neck squamous cell carcinoma (HNSCC). One hundred ninety-seven patients were included. All pretreatment saliva DNA samples were evaluated for the methylation status of the gene promoters by quantitative methylation-specific PCR. The main outcome measures were overall survival, local recurrence-free survival, and disease-free survival. In univariate analyses, the detection of hypermethylation of CCNA1, MGMT, and MINT31 was significantly associated with poor overall survival; the detection of hypermethylation of TIMP3 was significantly associated with local recurrence-free survival; and the detection of hypermethylation of MINT31 was significantly associated with poor disease-free survival. In multivariate analyses, detection of hypermethylation at any single marker was not predictive of overall survival in patients with HNSCC; detection of hypermethylation of TIMP3 in salivary rinse had an independent, significant association with local recurrence-free survival (HR = 2.51; 95% CI: 1.10-5.68); and none of the studied markers was significantly associated with disease-free survival. The detection of promoter hypermethylation of the seven genes in salivary rinse as an independent prognostic indicator of overall survival in patients with HNSCC was not validated. Detection of promoter hypermethylation of TIMP3 in pretreatment salivary rinse is independently associated with local recurrence-free survival in patients with HNSCC and may be a valuable salivary rinse biomarker for HNSCC recurrence.

MeSH Terms
Adult Aged Aged, 80 and over Apoptosis Regulatory Proteins/genetics Calcium-Calmodulin-Dependent Protein Kinases/genetics Carcinoma, Squamous Cell/genetics,mortality Cyclin A1/genetics Cyclin-Dependent Kinase Inhibitor p16/genetics DNA Methylation DNA Modification Methylases/genetics DNA Repair Enzymes/genetics Death-Associated Protein Kinases Disease-Free Survival Female Genes, DCC Head and Neck Neoplasms/genetics,mortality Humans Male Middle Aged Prognosis Promoter Regions, Genetic Saliva/metabolism Survival Analysis Tissue Inhibitor of Metalloproteinase-3/genetics Tumor Suppressor Proteins/genetics
Chemicals
Apoptosis Regulatory Proteins CCNA1 protein, human Cyclin A1 Cyclin-Dependent Kinase Inhibitor p16 Tissue Inhibitor of Metalloproteinase-3 Tumor Suppressor Proteins DNA Modification Methylases MGMT protein, human Death-Associated Protein Kinases Calcium-Calmodulin-Dependent Protein Kinases DNA Repair Enzymes
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Sun Wenyue
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
Zaboli David
Wang Hao
Liu Yan
Arnaoutakis Demetri
Khan Tanbir
Khan Zubair
Koch Wayne M
Califano Joseph A
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Article Info
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
Abbr.
Clin Cancer Res
ISSN
1557-3265
DOI
10.1158/1078-0432.CCR-11-2392
Published
2012-02-15
Epub
2012-00-06
Pages
1082-91
Language
English
Region
United States
NLM ID
9502500
PMCID
PMC3288549
Subset
IM
Grants
NIDCR NIH HHS · RC2DE020789 · United States
NIDCR NIH HHS · U54DE14257 · United States
NIDCR NIH HHS · RC2 DE020789-02 · United States
NIDCR NIH HHS · RC1 DE020324-02 · United States
NCI NIH HHS · U01 CA084986 · United States
NIDCR NIH HHS · RC1DE020324 · United States
NIDCR NIH HHS · RC2 DE020789 · United States
NIDCR NIH HHS · P50 DE019032 · United States
NCI NIH HHS · U01-CA084986 · United States
NIDCR NIH HHS · U54 DE014257 · United States
NIDCR NIH HHS · RC1 DE020324 · United States
NIDCR NIH HHS · P50DE019032 · United States
External Links
PubMed source DOI: 10.1158/1078-0432.CCR-11-2392 PMC Full Text View journal details
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