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...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2020-08-01
|
Series: | Cancers |
Subjects: | |
Online Access: | https://www.mdpi.com/2072-6694/12/9/2383 |
_version_ | 1797556131401302016 |
---|---|
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. |
first_indexed | 2024-03-10T16:58:29Z |
format | Article |
id | doaj.art-f512a5c2fe364652a4f172e3fd7e4b15 |
institution | Directory Open Access Journal |
issn | 2072-6694 |
language | English |
last_indexed | 2024-03-10T16:58:29Z |
publishDate | 2020-08-01 |
publisher | MDPI AG |
record_format | Article |
series | Cancers |
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 |
work_keys_str_mv | AT misoldo markeridentificationofthegradeofdysplasiaofintraductalpapillarymucinousneoplasminpancreaticcystfluidbyquantitativeproteomicprofiling AT hongbeomkim markeridentificationofthegradeofdysplasiaofintraductalpapillarymucinousneoplasminpancreaticcystfluidbyquantitativeproteomicprofiling AT dongyoonshin markeridentificationofthegradeofdysplasiaofintraductalpapillarymucinousneoplasminpancreaticcystfluidbyquantitativeproteomicprofiling AT joonhopark markeridentificationofthegradeofdysplasiaofintraductalpapillarymucinousneoplasminpancreaticcystfluidbyquantitativeproteomicprofiling AT haeryoungkim markeridentificationofthegradeofdysplasiaofintraductalpapillarymucinousneoplasminpancreaticcystfluidbyquantitativeproteomicprofiling AT youngminhan markeridentificationofthegradeofdysplasiaofintraductalpapillarymucinousneoplasminpancreaticcystfluidbyquantitativeproteomicprofiling AT jinyoungjang markeridentificationofthegradeofdysplasiaofintraductalpapillarymucinousneoplasminpancreaticcystfluidbyquantitativeproteomicprofiling AT youngsookim markeridentificationofthegradeofdysplasiaofintraductalpapillarymucinousneoplasminpancreaticcystfluidbyquantitativeproteomicprofiling |