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Quantitative proteomic analysis of pancreatic cyst fluid proteins associated with malignancy in intraductal papillary mucinous neoplasms

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Authors
Do, Misol; Han, Dohyun; Wang, Joseph I; Kim, Hyunsoo; Kwon, Wooil; Han, Youngmin; Jang, Jin-Young; Kim, Youngsoo
Issue Date
2018-04-18
Publisher
BioMed Central
Citation
Clinical Proteomics, 15(1):17
Keywords
Pancreatic cyst fuidIntraductal papillary mucinous neoplasmIPMNIPMN dysplasiaBiomarkercandidatesLC–MS/MS
Abstract
Background

The application of advanced imaging technologies for identifying pancreatic cysts has become widespread. However, accurately differentiating between low-grade dysplasia (LGD), high-grade dysplasia (HGD), and invasive intraductal papillary mucinous neoplasms (IPMNs) remains a diagnostic challenge with current biomarkers, necessitating the development of novel biomarkers that can distinguish IPMN malignancy.

Methods
Cyst fluid samples were collected from nine IPMN patients (3 LGD, 3 HGD, and 3 invasive IPMN) during their pancreatectomies. An integrated proteomics approach that combines filter-aided sample preparation, stage tip-based high-pH fractionation, and high-resolution MS was applied to acquire in-depth proteomic data of pancreatic cyst fluid and discover marker candidates for IPMN malignancy. Biological processes of differentially expressed proteins that are related to pancreatic cysts and aggressive malignancy were analyzed using bioinformatics tools such as gene ontology analysis and Ingenuity pathway analysis. In order to confirm the validity of the marker candidates, 19 cyst fluid samples were analyzed by western blot.

Results
A dataset of 2992 proteins was constructed from pancreatic cyst fluid samples. A subsequent analysis found 2963 identified proteins in individual samples, 2837 of which were quantifiable. Differentially expressed proteins between histological grades of IPMN were associated with pancreatic diseases and malignancy according to ingenuity pathway analysis. Eighteen biomarker candidates that were differentially expressed across IPMN histological grades were discovered—7 DEPs that were upregulated and 11 that were downregulated in more malignant grades. HOOK1 and PTPN6 were validated by western blot in an independent cohort, the results of which were consistent with our proteomic data.

Conclusions
This study demonstrates that novel biomarker candidates for IPMN malignancy can be discovered through proteomic analysis of pancreatic cyst fluid.
ISSN
1559-0275
Language
English
URI
http://hdl.handle.net/10371/141239
DOI
https://doi.org/10.1186/s12014-018-9193-1
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biomedical Sciences (대학원 의과학과)Journal Papers (저널논문_의과학과)
College of Medicine/School of Medicine (의과대학/대학원)Biomedical Engineering (의공학전공)Journal Papers (저널논문_의공학전공)
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