Abstract PR002: Transcriptomic influences of racial disparities in Black patients with pancreatic neuroendocrine tumors

Abstract

Abstract Introduction: There are known disparities in outcomes between Black and White patients with pancreatic neuroendocrine tumors (pNETs). Recently, Black patients have been shown to have higher rates of lymph node metastasis in smaller tumors than White patients, indicating possible differences in tumor biology. Numerous prognostic gene expression differences between racial groups have been reported in other cancers, but no such analysis has been conducted in pNETs. This study aims to evaluate pNET transcriptomes for differential expression that may be influencing racially disparate outcomes. Methods: Quality control of archival resected pNETs and demarcation of cancer cells were performed by a board-certified pathologist. Cells were laser microdissected from formalin-fixed, paraffin-embedded specimens, and RNA isolated. Sequencing was performed on an Illumina NextSeq550 at 30 million reads/sample. Alignments to the GRCh38 transcriptome annotation were performed using Salmon and differentially expressed genes (DEG’s) determined using DESeq2. Significant DEGs were determined by FDR-adjusted p-value (q-value; qv) < 0.05 and log2 fold-change (log2FC) ≥ ±2. Gene set enrichment analysis was performed using clusterProfiler and the Gene Ontology (GO) consortium gene sets. Ingenuity Pathway Analysis (IPA) was then conducted to determine regulator effect networks. Results: RNA sequencing was conducted on 14 and 16 grade and sex-matched primary pNETs from self-identified Black and White patients, respectively. Mean age was 51 for Black and 56 for White patients. 11/16 (69%) of White and 9/14 (64%) of Black patients were female. 8 Black patients and 8 White patients had grade 1 tumors, while 6 Black patients and 8 White patients had Grade 2 tumors. Metastatic disease was present in 4 Black and 5 White patients. Overall, 372 genes were significantly differentially expressed and 179 GO gene sets were differentially enriched between groups. Notably, among the top 10 most significantly enriched biological processes were: angiogenesis/blood vessel and vasculature development (qv=1.34e-07, normalized enrichment score [NES]=1.89), positive regulation of cell migration and locomotion (qv=1.34e-07, NES=1.91), and humoral immune response (qv= 9.8e-07, NES=-2.06). Among the top 5 regulator effect networks identified by IPA were: angiogenesis of lesion/cell movement of monocytes (consistency score [CS]=19.3), activation of blood cells (CS=18.9), and activation of cells (17.9). Conclusion: Numerous gene sets and pathways related to blood vessel development and cellular migration, representing key elements in the development of metastatic disease, are significantly enriched in pNETs from Black patients. Additionally, gene sets and pathways related to the immune response are downregulated in Black patients. These data indicate differences in tumor biology that may influence disparate outcomes reported in Black patients with pNETS. Sequencing of additional samples and incorporation of genetic ancestry are necessary to validate these findings. Citation Format: Brendon Herring, Rachael Guenter, Deepti Dhall, Herbert Chen, Clayton Yates, John Bart Rose. Transcriptomic influences of racial disparities in Black patients with pancreatic neuroendocrine tumors [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr PR002.