The Impact of Race on C-MYC Expression and Resulting Prognostic Implications in Head and Neck Squamous Cell Carcinoma

Abstract

<h3>Background</h3> Epidemiological data identifies race-based disparities in Black patients for head and neck squamous carcinoma (HNSCC) screening, detection, treatment, and survival. Although socioeconomic and environmental factors play a role in the existing racial disparities, HNSCC incidence and survival rates in the Black population cannot be attributed to these factors alone. Analyzing the molecular profiles of HNSCC tumors has the potential to help elucidate the mechanisms behind these disparities. The overexpression of the proto-oncogene C-MYC across racial demographics is of particular interest in this study given its association with poor outcomes in HNSCC. <h3>Materials and Methods</h3> To investigate the effect of race on survival of head and neck cancer, we examined HNSCC samples from 49 Black and 446 white patients in The Cancer Genome Atlas (TCGA). We used cox proportional hazard models and Kaplan Meier curves to identify the effect of race on HNSCC survival outcome. We then characterized the extent to which molecular alterations in Black patients impact their clinical outcomes. <h3>Results</h3> We found that Black patients lived significantly less disease-free months and had a poorer overall survival than white patients. Black patients showed a higher frequency of human papillomavirus (HPV)-negative than HPVpositive tumors compared to white patients. Black patients were found to suffer higher rates of metastasis and more aggressive lymph node involvement. Lastly, we found a significant enrichment of MYC signaling and amplifications in the tumors of Black patients compared to white patients. <h3>Conclusions</h3> This project uncovers novel data toward gaining an understanding of the racial disparities in HNSCC and advances the research aimed at eliminating these disparities. Unique tumor mutations and molecular signatures such as C-MYC could be used for more targeted, individualized screening, diagnostic, and treatment modalities to reduce outcome disparities in the Black population.