Abstract 780: Transcriptional profile of human pancreatic acinar ductal metaplasia

Abstract Aberrant acinar to ductal metaplasia (ADM), one of the earliest events involved in exocrine pancreatic cancer development, is typically studied using pancreata from transgenic mouse models. We used primary, human pancreatic acinar cells to evaluate the transcriptional profile during the course of ADM. Following six days of culture on Matrigel, acinar cells underwent morphological and molecular changes reminiscent of ADM. RNA was sequenced from 14 donor’s paired pancreata (day 0 and 6 of culture). Unsupervised hierarchical clustering demonstrated complete separation of the gene expression profile between culture day 0 (acinar phenotype) and day 6 (ductal phenotype). By and large, acinar-specific genes were downregulated in the samples from day 6 ADM while ductal-specific genes were upregulated. Using a gene set enrichment approach, we identified regulons that are involved in regulating ADM including downregulated, acinar-associated transcription factors (including PTF1A, RBPJL, and XBP1) and upregulated, ductal- and progenitor-associated transcription factors (SOX11, SOX4, and YAP1). The expression of pancreatic cancer associated genes significantly correlated with the gene expression/regulon activity observed in normal pancreas undergoing ADM. We reported a detail analysis of the transcriptional profile during human ADM. Our findings confirm that many ADM-related transcription factors and signaling pathways discovered in transgenic mouse models are applicable to human ADM and highlights the relevancy of in vitro models of pancreas plasticity using human tissue. Citation Format: Corey Melissa Perkins, Jinmai Jiang, Hesamedin Hakimjavadi, Julie K. Bray, Alyssa Gosling, Lais da Silva, Gamze Bulut, Jamel Ali, Wendy Setiawan, Martha Campbell-Thompson, Srikar Chamala, Thomas D. Schmittgen. Transcriptional profile of human pancreatic acinar ductal metaplasia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 780.