Pancreatic Cyst Glycopatterns as Potential Biomarkers for MCN and SCN

Abstract

Background & Aims: The pathophysiologies of malignant pancreatic cystic lesions, including mucinous cystic neoplasm (MCN), intraductal papillary mucinous neoplasm (IPMN), and mucinous cystic adenocarcinoma (MCA), are not fully understood, and no diagnostic or predictive biomarkers have been established. Glycosylation modifications on as many as 70% of all human proteins can reflect various pathological changes with high sensitivity. However, little is known about the alterations of glycosylation and glycoproteins in MCN. Methods: This study is based on the results of surgical pathology and cystic fluid cytology from 211 cases diagnosed with pancreatic cystic tumours. Liquid samples were obtained through endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA). Of the 75 cases, the cystic fluid of 35 cases was previously analysed by a lectin microarray, which was used to characterize the altered glycosylation between the MCN and SCN groups. We observed an increase in trimers and tetramers of GlcNAc, core (GlcNAc), multivalent sialic acid, Galβ1-3GalNAc, Terminal GalNAc, αGalNAc, Tn antigen, and GalNAcα1-3((Fucα1-2)) Gal (blood group A antigen) in the MCN group (P < 0.05). Of the remaining 40 cases, 20 were from the MCN group and 20 were from the SCN group; the accuracy of this distinction was verified. Moreover, altered glycan patterns on the surface of pancreatic cystic lesions were verified by lectin immunohistochemistry. This study is based on the results of increased binding signals in the MCN group by solanum tuberosum lectin (STL) and Bauhinia purpurea lectin (BPL), which bind glycoproteins, and the results of magnetic particle conjugateassisted LC-MS/MS analyses and bioinformatics analysis. The characteristics of lectin binding glycoproteins between STL and BPL demonstrated altered glycopatterns between the MCN and SCN groups. Each protein was evaluated in triplicate. Result: The ability of STLs and BPLs to bind glycoproteins in MCN/SCN cystic fluid was determined via quantitative analysis. Through bioinformatics analysis and STRING protein interaction diagrams, we concluded that the glycoproteins LAMC1, YWHAG, YWHAQ, YWHAZ, S100A11, HSPA5, LDHA, ACTB, KRT18, and ACTB were increased in MCN.Conclusions: We identified a panel of molecular markers and clinical features. These markers and features may be correlated with a significant increase in the mucin secretion of malignant epithelial cells. Funding Statement: This work was supported by the National Natural Science Foundation of Beijing (No.7182066). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: This prospective study was approved by the Department of Chinese PLA General Hospital Ethics Committee (Ethics NO. S2014-108-01).