Abstract PO-092: Development of an organoid assay for studying racial disparity in pancreatic acinar ductal metaplasia

Abstract

Abstract Blacks have higher rates of incidence and mortality of pancreatic cancer compared to Whites and non-White Hispanics. In an effort to identify a biological basis for this disparity, we propose examining the early events in the development of pancreatic cancer. The process by which pancreatic acini transdifferentiate into ductal epithelial cells (i.e. acinar ductal metaplasia or ADM) is one of the earliest events in the development of pancreatic ductal adenocarcinoma. We adapted the classic in vitro ADM assay, by which primary mouse pancreatic acini undergo ADM once plated onto the extracellular matrix matrigel, to an assay to culture and transdifferentiate human pancreatic organoids. We have received normal, human pancreatic acini from pancreatic islet transplantation centers from Black (n=8), White (n=19) and Hispanic (n=16) donors. The gender distribution was 29 males and 14 females. The acinar cells were cultured on matrigel and allowed to undergo ADM over a 5 to 6 day period. The number of ductal epithelial cells were microscopically counted and the rate of transdifferentiation was determined by kinetic modeling of the data. We have successfully cultured and transdifferentiated 40 of 43 human pancreatic acinar cells. Data from our study suggests that females undergo ADM at a faster rate than males and among the different races, the rate of acinar transdifferentiation decreases in the following order Blacks > Whites > non-White Hispanics. In summary, we demonstrate that women and Blacks have the highest rate of pancreatic transdifferentiation. Future studies include sequencing of the RNA isolated from the tissues to identify molecular drivers of acinar transdifferentiation and their impact on health disparities of pancreatic cancer. Citation Format: Alyssa Gosling, Jinmai Jiang, Corey M. Perkins, Yingwei Yao, Thomas D. Schmittgen. Development of an organoid assay for studying racial disparity in pancreatic acinar ductal metaplasia [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-092.