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MiRNA expression profiles in Pancreatic Cystic tumours and Pancreatic Cancer

ABSTRACT: MicroRNA (miRNA) expression profiles have been described in pancreatic ductal adenocarcinoma (PDAC), but these have not been compared with premalignant lesions. We wished to identify miRNA expression profiles in pancreatic cystic tumors with low malignant potential (serous microcystic adenomas) and high malignant potential (mucinous cystadenoma and intraductal papillary mucinous neoplasm (IPMN)) and compare these to PDAC and carcinoma-ex-IPMN (CEI). n= 20 samples Benign Pancreatic Cystic Tumour (n=7 Microcystic, n= 6 Mucinous, n= 7 IPMN) were compared with n= 9 samples of carcinoma ex IPMN and n= 14 samples of pancreatic cancer (adenocarcinoma) for known homo sapiens miRNAs (mirbase 13).

ORGANISM(S): Homo sapiens

SUBMITTER: Adam Frampton

PROVIDER: E-GEOD-29352 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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miRNA expression profiles in Pancreatic Cystic tumours and Pancreatic Cancer

Project description:MicroRNA (miRNA) expression profiles have been described in pancreatic ductal adenocarcinoma (PDAC), but these have not been compared with premalignant lesions. We wished to identify miRNA expression profiles in pancreatic cystic tumors with low malignant potential (serous microcystic adenomas) and high malignant potential (mucinous cystadenoma and intraductal papillary mucinous neoplasm (IPMN)) and compare these to PDAC and carcinoma-ex-IPMN (CEI).

2011-05-18 | GSE29352 | GEO

Kinase activities in pancreatic ductal adenocarcinoma with prognostic and therapeutic avenues

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Contributions of the Microbiome-Derived Metabolome for Risk Assessment and Prognostication of Pancreatic Cancer

Project description:<h4>BACKGROUND Increasing evidence implicates microbiome involvement in the development and progression of pancreatic ductal adenocarcinoma (PDAC). Studies suggest that reflux of gut or oral microbiota can lead to colonization in the pancreas, resulting in dysbiosis that culminates in release of microbial toxins and metabolites that potentiate an inflammatory response and increase susceptibility to PDAC. Moreover, microbe-derived metabolites can exert direct effector functions on precursors and cancer cells, as well as other cell types, to either promote or attenuate tumor development and modulate treatment response.</h4>CONTENT The occurrence of microbial metabolites in biofluids thereby enables risk assessment and prognostication of PDAC, as well as having potential for design of interception strategies. In this review, we first highlight the relevance of the microbiome for progression of precancerous lesions in the pancreas and, using liquid chromatography-mass spectrometry, provide supporting evidence that microbe-derived metabolites manifest in pancreatic cystic fluid and are associated with malignant progression of intraductal papillary mucinous neoplasm(s). We secondly summarize the biomarker potential of microbe-derived metabolite signatures for (a) identifying individuals at high risk of developing or harboring PDAC and (b) predicting response to treatment and disease outcomes.SUMMARY The microbiome-derived metabolome holds considerable promise for risk assessment and prognostication of PDAC.

2023-08-09 | MTBLS7260 | MetaboLights

Quantitative Proteomic Profiling for Predicting Grade of Dysplasia in Intraductal Papillary Mucinous Neoplasm using Pancreatic Cyst Fluid

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.

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Quantitative Proteomic Analysis of Pancreatic Cyst Fluid Proteins Associated with Malignancy in Intraductal Papillary Mucinous Neoplasms

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

Comprehensive Proteomic Characterization of Human Pancreatic Cyst Fluid from Intraductal Papillary Mucinous Neoplasm by LC-MS/MS

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

Transcriptome analysis of Arid1a-deficient IPMN and Brg1-deficient IPMN

Project description:Mutations of subunit genes of the SWI/SNF chromatin remodeling complexes were found in 12-23% of human Pancreatic Ductal Adenocarcinoma (PDAC). We previously showed that Brg1, a catalytic ATPase subunit of the SWI/SNF chromatin remodeling complexes, inhibits the formation of intraductal pancreatic mucinous neoplasms (IPMN) and IPMN-derived PDAC from ductal cells. On the other hand, ARID1A is the most frequent target of mutations in the SWI/SNF chromatin remodeling complexes in human PDAC. We found that Arid1a loss in the context of mutant Kras resulted in formation of IPMN and PDAC. We also found that the incidence of PDAC formation in Ptf1a-Cre; KrasG12D; Arid1af/f mice was markedly lower than that in Ptf1a-Cre; KrasG12D; Brg1f/f mice despite the similarities between Arid1a-deficient and Brg1-deficient IPMNs. We extracted total RNA from intraductal papillary mucinous neoplasms (IPMNs) in Ptf1a-Cre; KrasG12D; Arid1af/f and Ptf1a-Cre; KrasG12D; Brg1f/f mice and perform microarray analysis.

2018-03-31 | GSE96926 | GEO

Determination of pancreatic cyst fluids peptidome and proteome

Project description:Determination of pancreatic cyst fluids (PCF) peptidome and proteome in 5 distinct patient groups: malignant (CAs), intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs), serous cystic neoplasms (SCNs), and pseudocysts (PCs). The PCF <5kDa fraction, referred as the degradome, and proteome profiles were determined using a LTQ-Orbitrap Elite mass spectrometer coupled with a nanoAcquity LC system. Qualitative LC-MS/MS analyses were ran on pooled samples from all patients.

2019-01-14 | PXD005248 | Pride

Nuclear GSK-3β and Oncogenic KRas Promote Aqp5+ Pancreatic Duct Stem Cell Expansion

Project description:Intraductal papillary mucinous neoplasm (IPMN) represents the most commonly diagnosed precursor lesion of pancreatic ductal adenocarcinoma (PDA), however the cell-of-origin remains unclear. Herein, we show that pancreas-specific activation in mice of nuclear-targeted glycogen synthase kinase-3β and oncogenic KRasG12D leads to the loss of acinar cells, the expansion of ductal cells, and the rapid development of IPMN with low-grade dysplasia. RNA-sequencing identified the expression of several ductal stem cell lineage genes including the water channel AQP5. The Aqp5+ pancreatic ductal cell pool was proliferative, phenotypically distinct from mature pancreatic ductal cells, and deletion of AQP5 limited IPMN development. Significantly, Aqp5 is highly expressed in human IPMN along with GSK-3b suggesting that human preneoplastic lesions likely arise from the expansion of an Aqp5+ pancreatic ductal stem cell. Altogether, these data identify Aqp5+ ductal cells in the mouse and human pancreas as the likely cell-of-origin for IPMN.

2022-03-22 | GSE169618 | GEO

Metabolic profiling of cyst fluid from patients with Intraductal Pancreatic Mucinous Neoplasm (part II)

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

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