Yuefan Wang, Tung-Shing M. Lih, Jae W. Lee, Takao Ohtsuka, Yuto Hozaka, Mari Mino-Kenudson, Nazmi Volkan Adsay, Claudio Luchini, Aldo Scarpa, Ajay V. Maker, Grace E. Kim, Jorge Paulino, Lijun Chen, Jongmin Woo, Liyuan Jiao, Zhenyu Sun, Davina Goodman, Michael J. Pflüger, Nicholas J. Roberts, Hanno Matthaei, Ralph H. Hruban
{"title":"胰腺导管内乳头状肿瘤的多组学分析揭示了不同的模式和潜在的进展标记","authors":"Yuefan Wang, Tung-Shing M. Lih, Jae W. Lee, Takao Ohtsuka, Yuto Hozaka, Mari Mino-Kenudson, Nazmi Volkan Adsay, Claudio Luchini, Aldo Scarpa, Ajay V. Maker, Grace E. Kim, Jorge Paulino, Lijun Chen, Jongmin Woo, Liyuan Jiao, Zhenyu Sun, Davina Goodman, Michael J. Pflüger, Nicholas J. Roberts, Hanno Matthaei, Ralph H. Hruban","doi":"10.1016/j.ccell.2025.08.001","DOIUrl":null,"url":null,"abstract":"To enable early detection of pancreatic cancer from precancerous lesions, we analyze proteins and glycoproteins from 64 intraductal papillary mucinous neoplasms (IPMNs), 55 cyst fluid samples, 104 pancreatic ductal adenocarcinomas (PDACs), and various types of normal samples using mass spectrometry. High-grade IPMNs show enrichment of glycosylation level and tumor progression pathways compared to low-grade lesions. High-grade IPMN associated proteins, such as PLOD3, IRS2, LGALS9, and Trop-2, are identified and validated using immunolabeling and laser microdissection. Some high-grade associated proteins are also detected in pancreatic cyst fluids, which allows us to link proteins and glycoproteins expressed in neoplastic cells to clinically accessible biospecimens. Altered glycosylation level of extracellular matrix (ECM) proteins is observed in IPMNs compared to normal ducts. Additionally, we identify a subset of IPMNs with PDAC-like features, including elevated expression of ECM proteins. These findings offer insight into progression-associated proteins and emphasize the diagnostic and therapeutic potential of these proteins in pancreatic tumors.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"35 1","pages":""},"PeriodicalIF":44.5000,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Multi-omic profiling of intraductal papillary neoplasms of the pancreas reveals distinct patterns and potential markers of progression\",\"authors\":\"Yuefan Wang, Tung-Shing M. Lih, Jae W. Lee, Takao Ohtsuka, Yuto Hozaka, Mari Mino-Kenudson, Nazmi Volkan Adsay, Claudio Luchini, Aldo Scarpa, Ajay V. Maker, Grace E. Kim, Jorge Paulino, Lijun Chen, Jongmin Woo, Liyuan Jiao, Zhenyu Sun, Davina Goodman, Michael J. Pflüger, Nicholas J. Roberts, Hanno Matthaei, Ralph H. Hruban\",\"doi\":\"10.1016/j.ccell.2025.08.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"To enable early detection of pancreatic cancer from precancerous lesions, we analyze proteins and glycoproteins from 64 intraductal papillary mucinous neoplasms (IPMNs), 55 cyst fluid samples, 104 pancreatic ductal adenocarcinomas (PDACs), and various types of normal samples using mass spectrometry. High-grade IPMNs show enrichment of glycosylation level and tumor progression pathways compared to low-grade lesions. High-grade IPMN associated proteins, such as PLOD3, IRS2, LGALS9, and Trop-2, are identified and validated using immunolabeling and laser microdissection. Some high-grade associated proteins are also detected in pancreatic cyst fluids, which allows us to link proteins and glycoproteins expressed in neoplastic cells to clinically accessible biospecimens. Altered glycosylation level of extracellular matrix (ECM) proteins is observed in IPMNs compared to normal ducts. Additionally, we identify a subset of IPMNs with PDAC-like features, including elevated expression of ECM proteins. These findings offer insight into progression-associated proteins and emphasize the diagnostic and therapeutic potential of these proteins in pancreatic tumors.\",\"PeriodicalId\":9670,\"journal\":{\"name\":\"Cancer Cell\",\"volume\":\"35 1\",\"pages\":\"\"},\"PeriodicalIF\":44.5000,\"publicationDate\":\"2025-08-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Cell\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.ccell.2025.08.001\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Cell","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ccell.2025.08.001","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Multi-omic profiling of intraductal papillary neoplasms of the pancreas reveals distinct patterns and potential markers of progression
To enable early detection of pancreatic cancer from precancerous lesions, we analyze proteins and glycoproteins from 64 intraductal papillary mucinous neoplasms (IPMNs), 55 cyst fluid samples, 104 pancreatic ductal adenocarcinomas (PDACs), and various types of normal samples using mass spectrometry. High-grade IPMNs show enrichment of glycosylation level and tumor progression pathways compared to low-grade lesions. High-grade IPMN associated proteins, such as PLOD3, IRS2, LGALS9, and Trop-2, are identified and validated using immunolabeling and laser microdissection. Some high-grade associated proteins are also detected in pancreatic cyst fluids, which allows us to link proteins and glycoproteins expressed in neoplastic cells to clinically accessible biospecimens. Altered glycosylation level of extracellular matrix (ECM) proteins is observed in IPMNs compared to normal ducts. Additionally, we identify a subset of IPMNs with PDAC-like features, including elevated expression of ECM proteins. These findings offer insight into progression-associated proteins and emphasize the diagnostic and therapeutic potential of these proteins in pancreatic tumors.
期刊介绍:
Cancer Cell is a journal that focuses on promoting major advances in cancer research and oncology. The primary criteria for considering manuscripts are as follows:
Major advances: Manuscripts should provide significant advancements in answering important questions related to naturally occurring cancers.
Translational research: The journal welcomes translational research, which involves the application of basic scientific findings to human health and clinical practice.
Clinical investigations: Cancer Cell is interested in publishing clinical investigations that contribute to establishing new paradigms in the treatment, diagnosis, or prevention of cancers.
Insights into cancer biology: The journal values clinical investigations that provide important insights into cancer biology beyond what has been revealed by preclinical studies.
Mechanism-based proof-of-principle studies: Cancer Cell encourages the publication of mechanism-based proof-of-principle clinical studies, which demonstrate the feasibility of a specific therapeutic approach or diagnostic test.