The biological mechanisms of racial disparity in head and neck cancer

ABSTRACT This grant proposal addresses the disparities in oral/head and neck cancer outcomes, particularly among Black patients, by investigating molecular signatures and biomarkers for early detection and personalized treatment strategies. Oral squamous cell carcinoma (OSCC), a prevalent subtype of head and neck squamous cell carcinomas (HNSCCs), exhibits high mortality rates, with even poorer outcomes in Black patients. This disparity is not fully understood but is influenced by both socio-economic and biological factors. Notably, mutations, transcriptomic changes, and amplifications at specific genomic loci, such as 8q24.21, have been identified as potential contributors to the aggressiveness of OSCC in Black patients. The proposal outlines two specific aims to tackle this issue: 1) Develop a Tailored RNA Prognostic Model for Enhancing Oral Cancer Survival Predictions in Black Populations: This aim focuses on identifying gene expression signatures in Black HNSCC patients to predict early-stage OSCC at high-risk for disease progression. A prognostic model will be developed using transcriptomic, clinical, and histological data from internal and external cohorts of OSCC patients. 2) Contributions of 8q24.21 lncRNA Expression and Increased Copy Number to HNSCC Progression in Patients of African Ancestry: This aim investigates the role of lncRNAs at the 8q24.21 locus in modulating tumor aggressiveness, particularly in Black patients who are more likely to have locus amplification. The research will explore how 8q24.21 locus amplification impacts tumor proliferation, histopathology, gene expression, and progression, focusing on the CD44-Hippo axis for potential personalized medicine strategies. The proposed research is significant as it aims to identify high-risk patients within a well-defined Black patient population, uncovers previously unrecognized roles of 8q24.21 amplification and its lncRNAs in OSCC progression, and develops pre-clinical model systems for personalized cancer treatment. This multidisciplinary approach seeks to bridge the gap in survival outcomes and advance the understanding of OSCC biology in patients of African ancestry, potentially leading to better-targeted therapies and improved prognostic tools.