University of Florida College of Pharmacy scientists have uncovered early cancer-like molecular patterns hiding within healthy human pancreatic cells, providing new insight into the earliest stages of pancreatic cancer development.
In a study published in Cancer Research Communications, a journal of the American Association for Cancer Research, researchers analyzed pancreatic acinar cells from 69 organ donors. These digestive cells can undergo acinar ductal metaplasia, or ADM, a transformation that precedes pancreatic cancer. Until now, scientists did not know whether the molecular subtypes seen in pancreatic ductal adenocarcinoma — the most common form of pancreatic cancer — were also present in healthy pancreatic tissue.
Using RNA sequencing and advanced data analysis, the research team led by Thomas Schmittgen, Ph.D., discovered two distinct molecular patterns within normal acinar cells. One pattern resembled healthy pancreatic tissue, while the other displayed molecular signatures that parallel those described in pancreatic cancer. While their presence in healthy tissue does not imply a malignant state, these findings suggest that even in a healthy pancreas, some cells exhibit molecular signatures typically linked to cancer.
“Our data suggests that if their cells become mutated, certain individuals may be predisposed to develop pancreatic cancer more so than others,” said Schmittgen, professor and chair of pharmaceutics in the UF College of Pharmacy. “Future experiments will mutate key drivers of pancreatic cancer in cell cultures of a normal pancreas to learn if some tissues develop pancreatic cancer more readily than others.”
The study also examined whether a donor’s race and ancestry could influence early changes in pancreatic cells. The researchers found that individuals with higher African ancestry were more likely to show ADM-related molecular activity. These differences were not explained by diabetes, obesity, age, or gender, suggesting that ancestry-related biology plays an important role.
“Once diagnosed with pancreatic cancer, certain races, such as Hispanics, live longer than African Americans. Our experimental model showed that a normal pancreas from those of African ancestry displayed more aggressive molecular signatures compared to those of European or Hispanic genetic ancestry,” said Corey Perkins, Ph.D., lead co-author of the paper, a 2024 graduate of the UF College of Pharmacy and postdoctoral research fellow at the Dana-Farber Cancer Institute. “Dr. Schmittgen’s lab is currently conducting experiments to understand why some racial groups experience poorer outcomes, to translate these findings into personalized therapies for pancreatic cancer.”
Jinmai Jiang, Ph.D., a research assistant professor in the UF College of Pharmacy and co-first author, also made substantial contributions to the study. The Florida-California Cancer Research, Education and Engagement Health Center, or CaRE2, provided funding for the research.