Marker Identification of the Grade of Dysplasia of Intraductal Papillary Mucinous Neoplasm in Pancreatic Cyst Fluid by Quantitative Proteomic Profiling

The incidence of patients with pancreatic cystic lesions, particularly intraductal papillary mucinous neoplasm (IPMN), is increasing. Current guidelines, which primarily consider radiological features and laboratory data, have had limited success in predicting malignant IPMN. The lack of a definitiv...

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Main Authors: Misol Do, Hongbeom Kim, Dongyoon Shin, Joonho Park, Haeryoung Kim, Youngmin Han, Jin-Young Jang, Youngsoo Kim
Format: Article
Language:English
Published: MDPI AG 2020-08-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/12/9/2383
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author Misol Do
Hongbeom Kim
Dongyoon Shin
Joonho Park
Haeryoung Kim
Youngmin Han
Jin-Young Jang
Youngsoo Kim
author_facet Misol Do
Hongbeom Kim
Dongyoon Shin
Joonho Park
Haeryoung Kim
Youngmin Han
Jin-Young Jang
Youngsoo Kim
author_sort Misol Do
collection DOAJ
description The incidence of patients with pancreatic cystic lesions, particularly intraductal papillary mucinous neoplasm (IPMN), is increasing. Current guidelines, which primarily consider radiological features and laboratory data, have had limited success in predicting malignant IPMN. The lack of a definitive diagnostic method has led to low-risk IPMN patients undergoing unnecessary surgeries. To address this issue, we discovered IPMN marker candidates by analyzing pancreatic cystic fluid by mass spectrometry. A total of 30 cyst fluid samples, comprising IPMN dysplasia and other cystic lesions, were evaluated. Mucus was removed by brief sonication, and the resulting supernatant was subjected to filter-aided sample preparation and high-pH peptide fractionation. Subsequently, the samples were analyzed by LC-MS/MS. Using several bioinformatics tools, such as gene ontology and ingenuity pathway analysis, we detailed IPMNs at the molecular level. Among the 5834 proteins identified in our dataset, 364 proteins were differentially expressed between IPMN dysplasia. The 19 final candidates consistently increased or decreased with greater IPMN malignancy. CD55 was validated in an independent cohort by ELISA, Western blot, and IHC, and the results were consistent with the MS data. In summary, we have determined the characteristics of pancreatic cyst fluid proteins and discovered potential biomarkers for IPMN dysplasia.
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spelling doaj.art-f512a5c2fe364652a4f172e3fd7e4b152023-11-20T11:04:31ZengMDPI AGCancers2072-66942020-08-01129238310.3390/cancers12092383Marker Identification of the Grade of Dysplasia of Intraductal Papillary Mucinous Neoplasm in Pancreatic Cyst Fluid by Quantitative Proteomic ProfilingMisol Do0Hongbeom Kim1Dongyoon Shin2Joonho Park3Haeryoung Kim4Youngmin Han5Jin-Young Jang6Youngsoo Kim7Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Surgery, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Biomedical Engineering, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Pathology, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Surgery, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Surgery, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, KoreaThe incidence of patients with pancreatic cystic lesions, particularly intraductal papillary mucinous neoplasm (IPMN), is increasing. Current guidelines, which primarily consider radiological features and laboratory data, have had limited success in predicting malignant IPMN. The lack of a definitive diagnostic method has led to low-risk IPMN patients undergoing unnecessary surgeries. To address this issue, we discovered IPMN marker candidates by analyzing pancreatic cystic fluid by mass spectrometry. A total of 30 cyst fluid samples, comprising IPMN dysplasia and other cystic lesions, were evaluated. Mucus was removed by brief sonication, and the resulting supernatant was subjected to filter-aided sample preparation and high-pH peptide fractionation. Subsequently, the samples were analyzed by LC-MS/MS. Using several bioinformatics tools, such as gene ontology and ingenuity pathway analysis, we detailed IPMNs at the molecular level. Among the 5834 proteins identified in our dataset, 364 proteins were differentially expressed between IPMN dysplasia. The 19 final candidates consistently increased or decreased with greater IPMN malignancy. CD55 was validated in an independent cohort by ELISA, Western blot, and IHC, and the results were consistent with the MS data. In summary, we have determined the characteristics of pancreatic cyst fluid proteins and discovered potential biomarkers for IPMN dysplasia.https://www.mdpi.com/2072-6694/12/9/2383pancreatic cyst fluidintraductal papillary mucinous neoplasm (IPMN)mucinous cystic neoplasm (MCN)serous cystic neoplasm (SCN)biomarkersLC-MS/MS
spellingShingle Misol Do
Hongbeom Kim
Dongyoon Shin
Joonho Park
Haeryoung Kim
Youngmin Han
Jin-Young Jang
Youngsoo Kim
Marker Identification of the Grade of Dysplasia of Intraductal Papillary Mucinous Neoplasm in Pancreatic Cyst Fluid by Quantitative Proteomic Profiling
Cancers
pancreatic cyst fluid
intraductal papillary mucinous neoplasm (IPMN)
mucinous cystic neoplasm (MCN)
serous cystic neoplasm (SCN)
biomarkers
LC-MS/MS
title Marker Identification of the Grade of Dysplasia of Intraductal Papillary Mucinous Neoplasm in Pancreatic Cyst Fluid by Quantitative Proteomic Profiling
title_full Marker Identification of the Grade of Dysplasia of Intraductal Papillary Mucinous Neoplasm in Pancreatic Cyst Fluid by Quantitative Proteomic Profiling
title_fullStr Marker Identification of the Grade of Dysplasia of Intraductal Papillary Mucinous Neoplasm in Pancreatic Cyst Fluid by Quantitative Proteomic Profiling
title_full_unstemmed Marker Identification of the Grade of Dysplasia of Intraductal Papillary Mucinous Neoplasm in Pancreatic Cyst Fluid by Quantitative Proteomic Profiling
title_short Marker Identification of the Grade of Dysplasia of Intraductal Papillary Mucinous Neoplasm in Pancreatic Cyst Fluid by Quantitative Proteomic Profiling
title_sort marker identification of the grade of dysplasia of intraductal papillary mucinous neoplasm in pancreatic cyst fluid by quantitative proteomic profiling
topic pancreatic cyst fluid
intraductal papillary mucinous neoplasm (IPMN)
mucinous cystic neoplasm (MCN)
serous cystic neoplasm (SCN)
biomarkers
LC-MS/MS
url https://www.mdpi.com/2072-6694/12/9/2383
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