Analysis of Donor Pancreata Defines the Transcriptomic Signature and Microenvironment of Early Neoplastic Lesions

Date:	2 June 2023
PMID:	PMC10236159
Category:	N/A
Authors:	Eileen S. Carpenter; Ahmed M. Elhossiny; Padma Kadiyala; Jay Li; Jake McGue; Brian D. Griffith; Yaqing Zhang; Jacob Edwards; Sarah Nelson; Fatima Lima; Katelyn L. Donahue; Wenting Du; Allison C. Bischoff; Danyah Alomari; Hannah R. Watkoske; Michael Mattea; Stephanie The; Carlos E. Espinoza; Meredith Barrett; Christopher J. Sonnenday; Nicholas Olden; Chin-Tung Chen; Nicole Peterson; Valerie Gunchick; Vaibhav Sahai ; Arvind Rao; Filip Bednar; Jiaqi Shi; Timothy L. Frankel; Marina Pasca di Magliano
Abstract:

The adult healthy human pancreas has been poorly studied given the lack of indication to obtain tissue from the pancreas in the absence of disease and rapid postmortem degradation. We obtained pancreata from brain dead donors, thus avoiding any warm ischemia time. The 30 donors were diverse in age and race and had no known pancreas disease. Histopathologic analysis of the samples revealed pancreatic intraepithelial neoplasia (PanIN) lesions in most individuals irrespective of age. Using a combination of multiplex IHC, single-cell RNA sequencing, and spatial transcriptomics, we provide the first-ever characterization of the unique microenvironment of the adult human pancreas and of sporadic PanIN lesions. We compared healthy pancreata to pancreatic cancer and peritumoral tissue and observed distinct transcriptomic signatures in fibroblasts and, to a lesser extent, macrophages. PanIN epithelial cells from healthy pancreata were remarkably transcriptionally similar to cancer cells, suggesting that neoplastic pathways are initiated early in tumorigenesis.

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Acknowledgements:

The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute, or the National Institute of Health.

The Translational and Basic Science Research in Early Lesions (TBEL) Research Consortia is supported and funded by grants from the National Cancer Institute and the National Institutes of Health under the following award numbers:

Project Number:	Awardee Organization
U54CA274374	Fred Hutchinson Cancer Center
U54CA274375	Houston Methodist Research Institute
U54CA274370	Johns Hopkins University
U54CA274371	UT MD Anderson Cancer Center
U54CA274367	Vanderbilt University Medical Center