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

Autor: Do M; 1Department of Biomedical Sciences, Seoul National University College of Medicine, 28 Yeongeon-dong, Seoul, 110-799 Korea., Han D; 4Proteomics Core Facility, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Seoul, Korea., Wang JI; 2Department of Biomedical Engineering, Seoul National University College of Medicine, 28 Yeongeon-dong, Seoul, 110-799 Korea., Kim H; 2Department of Biomedical Engineering, Seoul National University College of Medicine, 28 Yeongeon-dong, Seoul, 110-799 Korea., Kwon W; 3Department of Surgery, Seoul National University College of Medicine, 28 Yeongeon-dong, Seoul, 110-799 Korea., Han Y; 3Department of Surgery, Seoul National University College of Medicine, 28 Yeongeon-dong, Seoul, 110-799 Korea., Jang JY; 3Department of Surgery, Seoul National University College of Medicine, 28 Yeongeon-dong, Seoul, 110-799 Korea., Kim Y; 1Department of Biomedical Sciences, Seoul National University College of Medicine, 28 Yeongeon-dong, Seoul, 110-799 Korea.; 2Department of Biomedical Engineering, Seoul National University College of Medicine, 28 Yeongeon-dong, Seoul, 110-799 Korea.
Jazyk: angličtina
Zdroj: Clinical proteomics [Clin Proteomics] 2018 Apr 18; Vol. 15, pp. 17. Date of Electronic Publication: 2018 Apr 18 (Print Publication: 2018).
DOI: 10.1186/s12014-018-9193-1
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje