Transcriptional Analyses of Acinar- And Ductal-Cell-Derived Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer, with one of the lowest 5-year survival rates at 10%. From mouse models, PDAC arises from acinar or ductal cells, and previous transcriptomic analyses have identified specific markers of acinar- and ductal-cell-derived PDAC. 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 showed gene expression profiles resembling the classical subtype, supporting previous studies, while the ductal-cell-derived PDAC had an expression of both classical and basal subtypes. Overall, our findings demonstrate that acinar and ductal tumors have similar expression profiles and further research is required to identify reliable traits of acinar- and ductal-cell-derived PDAC.