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MicroRNA-137 Promoter Methylation As An Etiologic and Prognostic Biomarker For Squamous Cell Carcinoma of the Head and Neck

Langevin, Scott M (2010) MicroRNA-137 Promoter Methylation As An Etiologic and Prognostic Biomarker For Squamous Cell Carcinoma of the Head and Neck. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Head and neck cancer accounted for 3.3% of incident malignancies and 2.0% of cancer-deaths in the US in 2009, the majority of which are squamous in origin. Thus, there is a need for novel biomarkers for early detection and prognosis of squamous cell carcinoma of the head and neck (SCCHN). MicroRNA-137 plays a role in cell cycle control through negative regulation of Cdk6, and has been reported to undergo promoter methylation in oral squamous cell carcinoma. Oral rinse is a non-invasive mode of DNA collection, which may have some utility in detection of promoter methylation. The primary goals of this research were to determine if miR-137 promoter methylation occurs in all SCCHN, including pharyngeal and laryngeal tumors, and whether it is detectable in oral rinse samples; and to assess miR-137 promoter methylation as an etiologic and prognostic biomarker for SCCHN. DNA was extracted from oral rinses from 99 SCCHN patients and 99 cancer-free control subjects and from tumor tissue of 67 SCCHN patients; paired oral rinses and tumor tissue was available for 64 of the SCCHN patients. Promoter methylation status of miR-137 was determined by methylation-specific PCR. We identified a strong association between miR-137 promoter methylation detected in oral rinses and SCCHN (OR = 4.80, 95% CI: 1.23-18.82). There was a strong positive association between female gender and miR-137 promoter methylation in oral rinse from SCCHN patients (OR = 5.30, 95% CI: 1.20-23.44) and an inverse association with body mass index (OR = 0.88, 95% CI: 0.77-0.99). Promoter methylation of miR-137 in tumor tissue was associated with poorer overall survival (HR = 3.68, 95% CI: 1.01-13.38). In spite of its low sensitivity (21.2%), miR-137 methylation detected in oral rinse may have future value in methylation panels for early diagnosis of SCCHN due to its high specificity (97.0%) and occurrence in early stage disease; and its detection in tumor tissue has promise as a prognostic marker. The identification of novel diagnostic and prognostic biomarkers for SCCHN such as miR-137 promoter methylation will significantly impact public health through the reduction of morbidity and mortality that occurs as a result of this disease.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Langevin, Scott Msml7925@msn.com
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee CoChairBunker, Clareann Hbunkerc@edc.pitt.eduBUNKERC
Committee CoChairTaioli, EmanuelaEmanuela.Taioli@downstate.edu
Committee MemberSobol, Robert Wrws9@pitt.eduRWS9
Committee MemberStone, Roslyn Aroslyn@pitt.eduROSLYN
Date: 28 June 2010
Date Type: Completion
Defense Date: 5 March 2010
Approval Date: 28 June 2010
Submission Date: 8 April 2010
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Epidemiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: epigenetics; biomarker; head and neck cancer; promoter methylation; microrna
Other ID: http://etd.library.pitt.edu/ETD/available/etd-04082010-161627/, etd-04082010-161627
Date Deposited: 10 Nov 2011 19:35
Last Modified: 15 Nov 2016 13:39
URI: http://d-scholarship.pitt.edu/id/eprint/6911

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