Abstract 6110: Computational exploration of genomic differences in Black patients treated with chemoradiation for head and neck squamous cell carcinoma (HNSCC)

Abstract Background: Black patients treated with chemoradiation for head and neck squamous cell carcinoma (HNSCC) experience significantly worse survival outcomes than White patients treated with the same modality. Our group aims to explore potential sociodemographic and biological factors undermining this differing response to therapy. Here, we present our computational findings of genomic differences in Black compared with White HNSCC patients receiving chemoradiation. Methods: We obtained gene expression, phenotype, and clinical datasets for the Cancer Genome Atlas (TCGA) HNSCC cohort from the UCSC Xena web browser. Of the 528 HNSCC patients, 131 (Black=13, White=118) of those receiving chemoradiation had gene expression, phenotype, and clinical data available. Our analysis included anatomic sites involving the oral cavity, hypopharynx, and larynx, and excluded the oropharynx. We performed differential gene expression analysis in Black compared with White (reference population) patients via edgeR in R studio (-log2FC < -1 or log2FC >1; p value < 0.05; FDR < 0.05). The Database for Annotation, Visualization, and Integrated Discovery (DAVID) webtool was used to identify significantly enriched molecular processes and pathways. Results: 462 genes were found to be significantly differentially expressed between Black and White HNSCC patients receiving chemoradiation. Of these genes, 198 were found to be higher in Black patients, and the most significant included JPH3, PCSK1N, DCUN1D5, CRYGS, and CCL7 (p < 0.005, FDR < 0.005). 264 were found to be lower in Black patients, with the most significant being KBTBD12, CMYA5, NEFH, LDB3, PYGM (p < 0.005, FDR < 0.005). Genes found to be higher in Black patients showed enrichment for processes such as EGFR tyrosine kinase inhibitor resistance (p < 0.005), drug metabolism (p < 0.005), and chemical carcinogenesis (p < 0.005). Genes found to be lower in Black patients showed enrichment for muscle-related processes such as myogenesis (p < 0.005), actin-binding (p < 0.005), muscle protein (p < 0.005), and hypertrophic cardiomyopathy (p < 0.005). Conclusion: In conclusion, using TCGA, we identified differentially expressed genes between Black and White HNSCC patients receiving chemoradiation. Moreover, these findings suggest that biological processes may differ in Black compared with White patients receiving chemoradiation, and this may dictate differing response to therapy. Additional studies will involve further computational analysis using other datasets for validation. Citation Format: Chayil C. Lattimore, Caretia J. Washington, Dejana Braithwaite, Shama D. Karanth, Kristianna M. Fredenburg. Computational exploration of genomic differences in Black patients treated with chemoradiation for head and neck squamous cell carcinoma (HNSCC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6110.