Systems‐Based Analysis of the Pancreatic Cancer‐Specific Glycome Reveals ST6GAL1 as a Driver of Human and Murine Disease

摘要: Pancreatic ductal adenocarcinoma (PDA) is the 3rd leading cause of cancer‐death in the U.S.. Glycans, such as CA‐19‐9, are biomarkers of PDA, but their roles in PDA biology are unclear. Herein, we utilized lectin microarray technology to compare the glycomes of human and murine PDA. We observed common aberrant patterns of glycosylation across both species, including increased levels of α‐2,3‐ and α‐2,6‐sialic acids, bisecting GlcNAc and poly‐LacNAc. Using single cell sequencing and histological data, we identified ST6GAL1, which underlies α‐2,6‐sialic acid, as a potential driver in human PDA. We created a novel mouse in which a pancreas‐specific genetic deletion of ST6GAL1 overlays the well‐established KC mouse model. Analysis of our model showed delayed cancer formation and a significant reduction in fibrosis. Our results highlight the utility of the KC model as an accurate reflection of …