Yuefan Wang, T Mamie Lih, Jae W Lee, Takao Ohtsuka, Yuto Hozaka, Mari Mino-Kenudson, N Volkan Adsay, Claudio Luchini, Aldo Scarpa, Ajay V Maker, Grace E Kim, Jorge Paulino, Lijun Chen, Liyuan Jiao, Zhenyu Sun, Davina Goodman, Michael J Pflüger, Nicholas J Roberts, Hanno Matthaei, Laura D Wood, Toru Furukawa, Hui Zhang, Ralph H Hruban
bioRxiv [Preprint]. 2024 Jul 7:2024.07.07.602385. doi: 10.1101/2024.07.07.602385.
In order to advance our understanding of precancers in the pancreas, 69 pancreatic intraductal papillary neoplasms (IPNs), including 64 intraductal papillary mucinous neoplasms (IPMNs) and 5 intraductal oncocytic papillary neoplasms (IOPNs), 32 pancreatic cyst fluid samples, 104 invasive pancreatic ductal adenocarcinomas (PDACs), 43 normal adjacent tissues (NATs), and 76 macro-dissected normal pancreatic ducts (NDs) were analyzed by mass spectrometry. A total of 10,246 proteins and 22,284 glycopeptides were identified in all tissue samples, and 756 proteins with more than 1.5-fold increase in abundance in IPMNs relative to NDs were identified, 45% of which were also identified in cyst fluids. The over-expression of selected proteins was validated by immunolabeling. Proteins and glycoproteins overexpressed in IPMNs included those involved in glycan biosynthesis and the immune system. In addition, multiomics clustering identified two subtypes of IPMNs. This study provides a foundation for understanding tumor progression and targets for earlier detection and therapies.