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Background: Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions of pancreatic ductal adenocarcinoma (PDAC). IPMNs are generally associated with high risk of developing malignancy and therefore need to be diagnosed and assessed accurately, once detected. Existing diagnostic methods are inadequate, and identification of efficient biomarker capable of detecting high-risk IPMNs is necessitated. Moreover, the mechanism of development of malignancy in IPMNs is also elusive., Methods: Gene expression meta-analysis conducted using 12 low-risk IPMN and 23 high-risk IPMN tissue samples. We have also listed all the altered miRNAs and long noncoding RNAs (lncRNAs), identified their target genes, and performed pathway analysis. We further enlisted cyst fluid proteins detected to be altered in high-risk or malignant IPMNs and compared them with fraction of differentially expressed genes secreted into cyst fluid., Results: Our meta-analysis identified 270 upregulated and 161 downregulated genes characteristically altered in high-risk IPMNs. We further identified 61 miRNAs and 14 lncRNAs and their target genes and key pathways contributing towards understanding of the gene regulation during the progression of the disease. Most importantly, we have detected 12 genes altered significantly both in cystic lesions and cyst fluid., Conclusion: Our study reports, for the first time, a meta-analysis identifying key changes in gene expression between low-risk and high-risk IPMNs and also explains the regulatory aspect through construction of a miRNA-lncRNA-mRNA interaction network. The 12-gene-signature could function as potential biomarker in cyst fluid for detection of IPMN with a high risk of developing malignancy., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Barsha Saha et al.)

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., Competing Interests: The authors declare that they have no conflicts of interest.