Study Identifies Key Markers In Pancreatic Cancer Progression
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Research published in the journal Cell Systems has identified novel molecular and cellular markers in the development of one of the most aggressive, deadly pancreatic cancers: pancreatic ductal adenocarcinoma (PDAC).
Pancreatic ductal adenocarcinoma arises from precancerous lesions in the pancreas. One of these lesion types, pancreatic intraepithelial neoplasias (PanINs), can appear in the pancreas years before they progress to invasive cancer. Because pancreatic intraepithelial neoplasias are so small, they cannot be detected by conventional clinical imaging tests.
By employing spatial transcriptomics a method for measuring and mapping gene expression within tissue sections the researchers created a three-part analysis pipeline to track changes in gene expression across samples from nine patients, including 14 pancreatic intraepithelial neoplasias and five rare, high-grade pancreatic intraepithelial neoplasias. They developed machine learning tools for imaging analysis (CODA) and for integrating these findings with single-cell datasets from pancreatic ductal adenocarcinoma, using innovative multi-omics integration methods such as CoGAPS (coordinated gene activity in pattern sets) and project R. The researchers have made their data and code publicly available to assist others in further exploring pancreatic cancer.
The results of their work provide new insights into the gene expression and spatial distribution of different types of cells in the precancerous environment around PanINs. These cells are cancer-associated fibroblasts (CAFs), including antigen-presenting cancer-associated fibroblasts CAFs.
Scientists also observed a shift from CAF-associated inflammatory signalling to increased cellular proliferation as pancreatic intraepithelial neoplasia progressed.
The three-way analysis revealed that some key features of pancreatic cancer were present in pancreatic intraepithelial neoplasias.
Reference: Bell, A. T. F., Mitchell, J. T., Kiemen, A. L., Lyman, M., Fujikura, K., Lee, J. W., Coyne, E., Shin, S. M., Nagaraj, S., Deshpande, A., Wu, P.-H., Sidiropoulos, D. N., Erbe, R., Stern, J., Chan, R., Williams, S., Chell, J. M., Ciotti, L., Zimmerman, J. W., Wirtz, D., Ho, W. J., Zaidi, N., Thompson, E., Jaffee, E. M., Wood, L. D., & Fertig, E. J. (2024). PanIN and CAF transitions in pancreatic carcinogenesis revealed with spatial data integration. Cell Systems. https://doi.org/10.1016/j.cels.2024.07.001
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