A revised model of clonal evolution of intraductal papillary mucinous neoplasm-related pancreatic carcinogenesis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE114163 | GEO | 2019/05/08
REPOSITORIES: GEO
Similar Datasets
Project description:Intraductal papillary mucinous neoplasm (IPMN) is a benign tumor that grows within the pancreatic ducts characterized by the production of thick mucinous fluid by surrounding tumor cells. IPMN is the most important precursor lesion for pancreatic cancer that is the fourth most common cause of cancer deaths. Differentiating between low-grade dysplasia (LGD), high-grade dysplasia (HGD), and invasive intraductal papillary mucinous neoplasms (IPMNs) remains a diagnostic challenge with current biomarkers, necessitating the development of novel biomarkers that can distinguish IPMN malignancy. We investigated differentially expressed proteins among pancreatic cyst fluids consisted of LGD, HGD, and invasive IPMN patients by using our novel proteomic strategy, and finally we discovered pancreatic cyst fluid protein marker candidates that can predict the malignant potential of IPMNs.
2018-05-01 | PXD008302 | Pride
Project description:A revised model of clonal evolution of intraductal papillary mucinous neoplasm-related pancreatic carcinogenesis
| PRJNA464916 | ENA
Project description:Intraductal papillary mucinous neoplasm (IPMN) is a duct-dilating precancerous lesion that grows in pancreatic ducts and is accompanied by the production of mucinous fluid. In recent years, its cystic fluid has been used molecularly for the differential diagnosis of other cystic tumors and malignancies. Thus, proteomic research of IPMN cyst fluid must be performed to identify an effective diagnostic biomarker. We examined the IPMN cyst fluid proteome using a novel proteomic strategy, combined with high-resolution LC-MS/MS. Although we did not deplete any high-abundance proteins, our dataset consistently detected thousands of proteins including pancreatic tumor markers, such as mucin family members, S100 proteins, and CEA-related proteins. In addition, we found 590 protein mutations through a variant sequence database search. Bioinformatics analyses were performed to determine biological functions and clinical meanings of canonical IPMN proteins and mutated proteins. Our proteomic platform and in-depth proteome dataset are valuable references that can be used in future studies.
2017-08-22 | PXD005671 | Pride
Project description:Circulating epithelial cells (CECs) were purified using a microfluidic device from healthy donors, patients bearing intraductal papillary mucinous neoplasms, or pancreatic ductal adenocarcinoma and their transcriptomes were sequenced.
2017-11-01 | GSE103152 | GEO
Project description:The increased number of pancreatic cyst lesions (PCLs) have been detected through the development of abdominal imaging techniques, such as computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasound (EUS). However, accurate classification of cystic lesions is difficult because of the lack of standardized diagnostic methods, and thus potentially unnecessary surgical resection has been performed on pancreatic cyst patients. Among four most common types of cystic lesions of pancreas, intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCN), serous cystic neoplasms (SCN), and solid pseudopapillary neoplasms (SPNs), IPMNs, the precursor lesion of pancreatic cancer, have been detected most frequently, and are subdivided into low-grade dysplasia (LGD), high-grade dysplasia (HGD), and invasive IPMN in accordance with their malignancy. To discover the potential biomarkers of the histological grades of IPMN, we investigated pancreatic cyst fluid proteins that are differentially expressed in accordance with the IPMN malignancy by LC-MS/MS analysis.
2020-09-06 | PXD016127 | Pride
Project description:Intraductal papillary mucinous neoplasm (IPMN) represents one precursor lesion of pancreatic ductal adenocarcinoma (PDA), but the cell-of-origin remains unclear. Here we describe a new mouse model in which pancreas-specific Cre activation of a nuclear glycogen synthase kinase-3β transgene is combined with oncogenic KRas (referred to as KNGC). KNGC mice show accumulation of neoplastic ductal cells at 4-weeks that progressively develop into IPMN with low-grade dysplasia in advanced age. RNA-sequencing identified expression of several genes found in the terminal duct cell lineage including Agr2 and Aqp5. Interestingly, Aqp5, a water channel, was found to be required for the development of IPMN lesions in KNGC mice. Staining of human IPMN samples indicates that these preneoplastic lesions also arise from expansion of the terminal duct population. Altogether, these data highlight the utility of the KNGC model for understanding the biology of IPMN and potential utility in defining predictive biomarkers of IPMN – PDA development.
2022-03-22 | GSE153548 | GEO
Project description:The pancreatic cyst fluids were collected using a syringe aspiration of the cyst fluid immediately after surgical resection of the lesion. The cyst fluid were then aliquoted and stored in -80C freezer until ready to use. We plan on performing untargeted metabolomics analysis and unknown lipid analysis and identification on these pancreatic cyst fluid to find potential biomarkers that correlate with histopathological assessment and clinical behavior of these cystic lesions and thus to guide clinical management of patients. Abbreviations: IPMN - Intraductal Pancreatic Mucinous Neoplasm; MCN - mucinous cystic neoplasm; SCA - serous cystadenoma.
2017-07-14 | ST000823 | MetabolomicsWorkbench
Project description:Purpose: The diagnosis of high grade intraductal papillary mucinous neoplasm (IPMN) is difficult to distinguish from low grade IPMN. The aim of this study was to identify potential markers for the discrimination of high grade and invasive IPMN from low and moderate grade IPMN. Experimental Design: Laser capture microdissection was used to isolate distinct foci of low grade, moderate grade, high grade, and invasive IPMN from paraffin embedded archival tissue from 14 patients who underwent resection for IPMN. Most samples included multiple grades in the same specimen. Affymetrix Human Exon microarrays were used for gene expression analysis to compare low and moderate grade (LMD) IPMN to high grade and invasive (HgInv) IPMN. Results: When comparing samples of LMD dysplasia (n=15) to those demonstrating HgInv (n=13), 62 genes were identified as showing significant changes in expression (p≤0.05 and a 2-fold cutoff), with up-regulation of 41 in HgInv IPMN and down-regulation in 21. Changes in gene expression are associated with biological processes related to malignant behavior including cell motion, cell proliferation, response to hypoxia, and epithelial to mesenchymal transition. Hierarchical clustering analysis demonstrated the ability of these 62 differentially expressed genes to distinguish between LMD and HgInv samples. In addition, altered signaling in several TGFβ-related pathways was exhibited in the progression of IPMN to malignancy. Conclusions: This study identifies a set genes associated with the progression of IPMN to malignancy. These genes are potential markers that could be used to identify IPMN requiring surgical resection. Using laser capture microdissection, distinct foci of low (n=10), moderate (n=5), and high grade dysplasia (n=6) as well as invasive carcinoma (n=7) were isolated from paraffin embedded archival tissue of 14 patients who underwent resection for IPMN. Gene expression data from Affymetrix Human Exon 1.0ST microarrays was utilized to compare low and moderate grade IPMN to high and invasive IPMN.
2011-12-01 | E-GEOD-26647 | biostudies-arrayexpress
Project description:Purpose: The diagnosis of high grade intraductal papillary mucinous neoplasm (IPMN) is difficult to distinguish from low grade IPMN. The aim of this study was to identify potential markers for the discrimination of high grade and invasive IPMN from low and moderate grade IPMN. Experimental Design: Laser capture microdissection was used to isolate distinct foci of low grade, moderate grade, high grade, and invasive IPMN from paraffin embedded archival tissue from 14 patients who underwent resection for IPMN. Most samples included multiple grades in the same specimen. Affymetrix Human Exon microarrays were used for gene expression analysis to compare low and moderate grade (LMD) IPMN to high grade and invasive (HgInv) IPMN. Results: When comparing samples of LMD dysplasia (n=15) to those demonstrating HgInv (n=13), 62 genes were identified as showing significant changes in expression (p≤0.05 and a 2-fold cutoff), with up-regulation of 41 in HgInv IPMN and down-regulation in 21. Changes in gene expression are associated with biological processes related to malignant behavior including cell motion, cell proliferation, response to hypoxia, and epithelial to mesenchymal transition. Hierarchical clustering analysis demonstrated the ability of these 62 differentially expressed genes to distinguish between LMD and HgInv samples. In addition, altered signaling in several TGFβ-related pathways was exhibited in the progression of IPMN to malignancy. Conclusions: This study identifies a set genes associated with the progression of IPMN to malignancy. These genes are potential markers that could be used to identify IPMN requiring surgical resection.
2011-12-01 | GSE26647 | GEO
Project description:The host antitumor immunity changes drastically during carcinogenesis. Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas is a precursor lesion of pancreatic cancer and progresses according to adenoma-carcinoma sequence. We found that the host antitumor immune reaction changes from an immune response to immune tolerance between intraductal papillary-mucinous adenoma (IPMA) and intraductal papillary-mucinous carcinoma (IPMC). In order to determine molecules affecting intraepithelial DC infiltration in IPMNs during multistep carcinogenesis, we examined the gene-expression profiles of entire transcripts of neoplastic cells at different stages.
2010-12-23 | GSE19650 | GEO