Abstract 3651: Mutational analysis and spatial phenotyping to decipher racial disparities in pancreatic adenocarcinoma

Abstract Background: Pancreatic cancer has a 5-year survival of only 12%. This is due to the lack of effective treatments and virtually no early detection methods. To compound this already poor prognosis, African Americans face a 20% higher incidence and worse mortality compared to non-African American patients. With a substantial portion of the data and tools employed for studying pancreatic cancer failing to adequately represent this demographic we aim to gain more insight into the differences associated with worse outcomes for African Americans with pancreatic cancer. To achieve this, we conducted an in-depth analysis of tumor mutational burden using whole exome sequencing and the cutting-edge PhenoCycler®-Fusion 2.0 spatial biology platform, to uncover disparities in spatial immune and metabolic phenotypes. Methods: Using an ultrahigh-plex discovery panel of markers encompassing cell lineage, immune checkpoints, tissue architecture, activation, metabolism, proliferation, and stress, we sought to analyze the differences in spatial phenotypes, cellular neighborhoods and functional pathways across the two groups. Additionally, we performed laser capture microdissection on a cohort of patients containing equal numbers of African American and non-African American pancreatic cancer samples. Tumor, stroma, and adjacent normal areas were identified by a board-certified pathologist. These annotations were used to laser capture on 10-micron sections with 7 sections for each patient. We performed whole exome sequencing on these sections and different areas and compared between groups. Results: Through our investigation using these two technologies, we can find differences in the tumor microenvironment between African Americans and non-African Americans. We can see potential associations in the increased mortality and incidence of this group while also building a foundation of racially diverse data to be used for future studies. Whole exome sequencing has revealed distinct mutational patterns among African American patients, involving common genes that exhibit unique mutation profiles when compared to those previously observed in non-African American patients. Moreover, whole-slide spatial phenotyping reveals the differential tumor-immune landscapes and the key cellular and molecular niches that contribute to tumor progression and prognosis. These findings underscore the imperative need for a more systems biology exploration of the variations within these groups, with the aim of developing more effective and personalized treatment approaches. Citation Format: Daniel James Salas-Escabillas, Ning Ma, Bassem Ben Cheikh, Aditya Pratapa, Thais Pichardo, Kyra Langley, Julie Clark, Nina Steele, Niyati Jhaveri, David Kwon, Howard C. Crawford. Mutational analysis and spatial phenotyping to decipher racial disparities in pancreatic adenocarcinoma [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 3651.