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.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-04082010-161627 |
| Date | 28 June 2010 |
| Creators | Langevin, Scott M |
| Contributors | Roslyn A Stone, Robert W Sobol, PhD, Clareann H Bunker, PhD, Emanuela Taioli |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-04082010-161627/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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