Cyst fluid glycoproteins accurately distinguishing malignancies of pancreatic cystic neoplasm

Ming Cui; Ya Hu; Zejian Zhang; Tianqi Chen; Menghua Dai; Qiang Xu; Junchao Guo; Taiping Zhang; Quan Liao; Jun Yu; Yupei Zhao

doi:10.1038/s41392-023-01645-8

Signal Transduction and Targeted Therapy (Oct 2023)

Cyst fluid glycoproteins accurately distinguishing malignancies of pancreatic cystic neoplasm

Ming Cui,
Ya Hu,
Zejian Zhang,
Tianqi Chen,
Menghua Dai,
Qiang Xu,
Junchao Guo,
Taiping Zhang,
Quan Liao,
Jun Yu,
Yupei Zhao

Affiliations

Ming Cui: Department of General Surgery, Key Laboratory of Research in Pancreatic Tumor, State Key Laboratory of Complex Severe and Rare Disease, National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Ya Hu: Department of General Surgery, Key Laboratory of Research in Pancreatic Tumor, State Key Laboratory of Complex Severe and Rare Disease, National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Zejian Zhang: Department of Medical Research Center, State Key Laboratory of Complex Severe and Rare Disease, National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Tianqi Chen: Department of Medical Research Center, State Key Laboratory of Complex Severe and Rare Disease, National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Menghua Dai: Department of General Surgery, Key Laboratory of Research in Pancreatic Tumor, State Key Laboratory of Complex Severe and Rare Disease, National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Qiang Xu: Department of General Surgery, Key Laboratory of Research in Pancreatic Tumor, State Key Laboratory of Complex Severe and Rare Disease, National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Junchao Guo: Department of General Surgery, Key Laboratory of Research in Pancreatic Tumor, State Key Laboratory of Complex Severe and Rare Disease, National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Taiping Zhang: Department of General Surgery, Key Laboratory of Research in Pancreatic Tumor, State Key Laboratory of Complex Severe and Rare Disease, National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Quan Liao: Department of General Surgery, Key Laboratory of Research in Pancreatic Tumor, State Key Laboratory of Complex Severe and Rare Disease, National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Jun Yu: Department of Medicine, Oncology, and Surgery, Johns Hopkins University School of Medicine
Yupei Zhao: Department of General Surgery, Key Laboratory of Research in Pancreatic Tumor, State Key Laboratory of Complex Severe and Rare Disease, National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

DOI: https://doi.org/10.1038/s41392-023-01645-8
Journal volume & issue: Vol. 8, no. 1
pp. 1 – 10

Abstract

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Abstract Pancreatic cystic neoplasms (PCNs) are recognized as precursor lesions of pancreatic cancer, with a marked increase in prevalence. Early detection of malignant PCNs is crucial for improving prognosis; however, current diagnostic methods are insufficient for accurately identifying malignant PCNs. Here, we utilized mass spectrometry (MS)-based glycosite- and glycoform-specific glycoproteomics, combined with proteomics, to explore potential cyst fluid diagnostic biomarkers for PCN. The glycoproteomic and proteomic landscape of pancreatic cyst fluid samples from PCN patients was comprehensively investigated, and its characteristics during the malignant transformation of PCN were analyzed. Under the criteria of screening specific cyst fluid biomarkers for the diagnosis of PCN, a group of cyst fluid glycoprotein biomarkers was identified. Through parallel reaction monitoring (PRM)-based targeted glycoproteomic analysis, we validated these chosen glycoprotein biomarkers in a second cohort, ultimately confirming N-glycosylated PHKB (Asn-935, H5N2F0S0; Asn-935, H4N4F0S0; Asn-935, H5N4F0S0), CEACAM5 (Asn-197, H5N4F0S0) and ATP6V0A4 (Asn-367, H6N4F0S0) as promising diagnostic biomarkers for distinguishing malignant PCNs. These glycoprotein biomarkers exhibited robust performance, with an area under the curve ranging from 0.771 to 0.948. In conclusion, we successfully established and conducted MS-based glycoproteomic analysis to identify novel cyst fluid glycoprotein biomarkers for PCN. These findings hold significant clinical implications, providing valuable insights for PCN decision-making, and potentially offering therapeutic targets for PCN treatment.

Published in Signal Transduction and Targeted Therapy

ISSN: 2059-3635 (Online)
Publisher: Nature Publishing Group
Country of publisher: United Kingdom
LCC subjects: Medicine; Science: Biology (General)
Website: http://www.nature.com/sigtrans/

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