Abstract
Background. Advances in imaging improve the detection of malignant pancreatic cystic including mucinous cystic neoplasm (MCN), intraductal papillary mucinous neoplasm (IPMN), and mucinous cystic adenocarcinoma (MCA), but the distinction between benign and malignant lesions remains a problem. In an effort to establish glycopatterns as potential biomarkers for differential diagnosis between MCN and SCN, we systematically investigated the alterations of glycopatterns in cystic fluids for both SCN and MCN. Methods. Among the 75 patients enrolled, 37 were diagnosed as MCN and 38 as SCN based on histology. Lectin microarray analysis was performed on each sample, and the fluorescence intensity was used to obtain the fold-change. Then, mixed cyst fluids of MCN group and SCN group were cross bonded with magnetic particles coupled by Lectin STL and WGA, respectively. Hydrophilic interaction liquid chromatography (HILIC) enrichment was performed, liquid chromatography (LC)/mass spectrometry (MS) analysis and bioinformatical analysis was conducted to find the differential glycoproteins between MCNs and SCNs. Results. Through analysis of lectin microarray between MCNs and SCNs, stronger lectin signal patterns were assigned to Lectin WFA, DBA, STL, WGA, and BPL; and weaker signal patterns were assigned to Lectin PTL-I, Con A, ACA, and MAL-I. The glycoproteins were enriched by STL or WGA-coupled magnetic particles. Furthermore, the 10 identified correspondding genes were found to be significantly elevated in the mucinous cystadenoma: CLU, A2M, FGA, FGB, FGG, PLG, SERPINA1, SERPING1, C5, C8A, and C9. Bioinformatics analysis revealed that the above genes may activate the KEGG pathway: immune complement system. Conclusion. This study shows changes in glycopatterns and glycoproteins are associated with MCNs and SCNs.
Highlights
Based on imaging studies, pancreatic cystic neoplasms (PCNs) are being diagnosed with increasing frequency, the prevalence of PCNs in the general population is estimated to be between 2.6% and 45% [1,2,3,4]
We report 75 cases, with in the mucinous cystic neoplasm (MCN) group and in the serous cystic neoplasm (SCN) group, using lectin microarrays to quantitatively analyse the differential types of glycan patterns and using the magnetic particles of labelled lectins to enrich the glycoproteins
Lyophilized peptide samples were resuspended in 0.1% formic acid (FA) and separated on a reversed-phase C18 column in-house packed analytical column (75 μm ID×20 cm, 3 μm, ReproSilPur C18 AQ, Dr Maisch GmbH, Germany) using mobile phase A (0.1% FA in water) and mobile phase B (0.1% FA in acetonitrile) with a gradient (5-8% B, 8 min; 8-22% B, 50 min; 22-32% B, 12 min; 32-95% B, 1 min; 95% B, 7 min) at a flow rate of 280 nL/min
Summary
Pancreatic cystic neoplasms (PCNs) are being diagnosed with increasing frequency, the prevalence of PCNs in the general population is estimated to be between 2.6% and 45% [1,2,3,4]. Clinical differential diagnosis between the potential malignant pancreatic mucinous cystic neoplasm (MCN) and the mostly benign serous cystic neoplasm (SCN) remains challenging [5,6,7,8]. Carcinoembryonic antigen (CEA) >192ng/L in cyst fluids could be reports on potential malignant PCNs. Mostly, gene mutations of KRAS at codon 12,13 are hallmark genetic alterations of pancreatic ductal adenocarcinoma (PDAC), and GNAS codon 201 mutations are hallmark genetic alterations of IPMNs [13, 14]. Mixed cyst fluids of MCN group and SCN group were cross bonded with magnetic particles coupled by Lectin STL and WGA, respectively. Hydrophilic interaction liquid chromatography (HILIC) enrichment was performed, liquid chromatography (LC)/mass spectrometry (MS) analysis and bioinformatical analysis was conducted to find the differential glycoproteins between MCNs and SCNs. Results. This study shows changes in glycopatterns and glycoproteins are associated with MCNs and SCNs
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