Abstract 7046: Proteogenomic and immunologic profiles of head and neck cancer patients of African ancestry

Abstract Blacks/African Americans (BAAs) with head and neck squamous cell carcinoma (HNSCC) have worse survival than Whites. However, the complex molecular biomarkers and signatures of HNSCC among BAAs and molecular distinction associated with HNSCC disparities are largely unknown. Here we show the results of a multi-omics analysis of 500 patients (48 BAAs and 452 Whites). Comparative analyses between the racial groups were performed at the level of genomics, pathways, molecular subtype, tumor immune infiltration, protein alterations and prognosis. We found that overall survival in BAAs with HPV-unrelated HNSCC is significantly shorter than in White patients. Ancestry-related differential mutation spectrum, DNA methylation, gene and protein expression pattern and immune infiltration landscape were identified. Particularly, FAT1 mutation is significantly associated with its gene expression in BAA HNSCC and poor overall survival in this group. In BAA HNSCC, SALL3 gene expression is positively associated with its gene CNVs, while RTP4 gene expression is inversely correlated with its methylation. High EGFRₚY1068 and RAD50 levels correlate with poor prognosis in BAAs with HNSCC. The immune infiltration enrichment scores of Th17 cells, activated dendritic cells, monocytes and neutrophils in BAA HNSCC were significantly lower than those in White HNSCC. By combining multi-omics analysis and data validation using in-house-made tumor tissue arrays, this study comprehensively elucidates the genetic landscape, immune response, and tumor biology in BAA and White HNSCC patients, providing a molecular basis for future research in identifying appropriate screening modalities and therapeutic interventions leading to improved outcomes in BAAs with HNSCC. Citation Format: Fan Yang, Fanghui Chen, Chloe Shay, Nabil F. Saba, Yong Teng. Proteogenomic and immunologic profiles of head and neck cancer patients of African ancestry 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 (6Suppl): Abstract nr 7046.