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Chu, Ken H.

University of British Columbia

Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer, with one of the lowest 5-year survival rates at 10% across all cancers. In mouse models, PDAC arises from acinar or ductal cells, and previous transcriptomic analyses have identified specific markers of acinar- and ductal-cell-derived PDAC. However, although we have developed a more comprehensive understanding of the cellular origin of PDAC from mouse models, this knowledge has not been effectively utilized to classify patient tumors. Here, we generated mouse models where acinar or ductal cells, using Ptf1aCreER or Sox9CreER, respectively, expressed oncogenic Kras in the absence of Trp53 or Pten and formed PDAC tumors. Using both in vivo and in vitro methods, we reveal that acinar- and ductal-cell-derived tumors are largely similar to one another with small differences in gene expression. We also found variability in the expression levels of previously predicted markers of cellular origin and propose a more comprehensive set of transcriptomic markers. Moreover, our acinar-cell-derived PDAC samples showed enrichment in the classical subtype, consistent with previous studies, while basal subtype genes were expressed at similar levels across both cellular origins. Overall, our findings demonstrate that acinar and ductal tumors have similar expression profiles and require further research to elucidate the reliability of markers for diagnostic use.

Text

2024-08-06

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/88875

Cell and Developmental Biology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/