Date of Award

Spring 5-2-2018

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Biology

Abstract

Human papillomavirus (HPV)-negative (-ve) oropharyngeal squamous cell carcinomas (OPSCCs) are associated with poorer overall survival (OS) compared to HPV-positive (+ve) OPSCCs. The major obstacle to improving outcomes of HPV -ve patients is the absence of good biomarkers. Herein, we investigated the role of centrosome amplification (CA) as a prognostic marker in HPV –ve OPSCCs. We first quantitatively assessed CA in OPSCC tumor samples and found that HPV -ve OPSCCs exhibit higher CA compared to HPV +ve OPSCCs, and was associated with poor OS even after adjusting for potentially confounding variables. Further, the expression of genes associated with hypoxia and CA was significantly higher in HPV -ve OPSCCs than in HPV +ve OPSCCs. We further uncovered a mechanism by which hypoxia-induced HIF-1α downregulates miR-34a resulting in cyclin D1 overexpression and rampant CA in HPV -ve OPSCCs. Our findings demonstrate that assessment of CA may aid in therapeutic decision-making for these patients.

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