Abstract
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.
Highlights
The incidental detection of pancreatic cystic lesions (PCLs) has increased in recent years due to the implementation of various screening methods and the advancement of medical imaging technologies, such as magnetic resonance imaging (MRI), computed tomography (CT), and endoscopic ultrasound (EUS) [1,2,3,4,5]
A mass mass spectrometry-based spectrometry-based method, method, based based on on our our previous previous study, study, was was used used to to analyze analyze aa cohort cohort of cyst fluid fluid samples samples to tomeasure measurethe thechanges changesininprotein proteinexpression expressionwith with respect progression of cyst respect to to thethe progression of of
The differentially expressed proteins (DEPs) were associated with biological functions that were related to pancreatic cancer, malignancy, and molecular secretion
Summary
The incidental detection of pancreatic cystic lesions (PCLs) has increased in recent years due to the implementation of various screening methods and the advancement of medical imaging technologies, such as magnetic resonance imaging (MRI), computed tomography (CT), and endoscopic ultrasound (EUS) [1,2,3,4,5]. LGD is considered primarily to be amenable to active surveillance, whereas the lesions in HGD and invasive IPMN require surgical intervention [7,8], necessitating the accurate classification of cystic lesions for appropriate patient management. The standard for determining whether to conduct active surveillance or surgical intervention and the diagnostic accuracy in determining IPMN grade differ between guidelines
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