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(Unpublished)
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: |
|
ETD Committee: |
|
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: |
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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