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

Cyst fluid glycoproteins accurately distinguishing malignancies of pancreatic cystic neoplasm

Signal Transduct Target Ther. 2023 Oct 18;8(1):406. doi: 10.1038/s41392-023-01645-8.

Authors

Ming Cui^#¹, Ya Hu^#¹, Zejian Zhang², Tianqi Chen², Menghua Dai¹, Qiang Xu¹, Junchao Guo¹, Taiping Zhang¹, Quan Liao¹, Jun Yu^{3

4}, Yupei Zhao⁵

Affiliations

¹ 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, Beijing, 100730, China.
² 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, Beijing, 100730, China.
³ Department of Medicine, Oncology, and Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21224, USA.
⁴ Pancreas center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
⁵ 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, Beijing, 100730, China. zhao8028@263.net.

^# Contributed equally.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cyst Fluid
Glycoproteins
Humans
Neoplasms, Cystic, Mucinous, and Serous*
Pancreatic Cyst* / diagnosis
Pancreatic Cyst* / epidemiology
Pancreatic Cyst* / pathology
Pancreatic Neoplasms* / diagnosis
Pancreatic Neoplasms* / pathology
Proteomics

Substances

Glycoproteins