Dataset Information

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

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cyst

DISEASE(S): Pancreatic Intraductal Papillary-mucinous Neoplasm

SUBMITTER: Dohyun Han

LAB HEAD: Dohyun Han

PROVIDER: PXD005671 | Pride | 2017-08-22

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20150207_1st_cyst_pellet_long_1.raw	Raw
	20150207_1st_cyst_pellet_long_2.raw	Raw
	20150207_1st_cyst_pellet_long_3.raw	Raw
	20150207_1st_cyst_spnt_long_1.raw	Raw
	20150207_1st_cyst_spnt_long_2_re.raw	Raw

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Publications

Proteome characterization of human pancreatic cyst fluid from intraductal papillary mucinous neoplasm by liquid chromatography/tandem mass spectrometry.

Park Joonho J Han Dohyun D Do Misol M Woo Jongmin J Wang Joseph I JI Han Youngmin Y Kwon Wooil W Kim Sun-Whe SW Jang Jin-Young JY Kim Youngsoo Y

Rapid communications in mass spectrometry : RCM 20171001 20

<h4>Rationale</h4>In recent years, the molecular components of pancreatic cyst fluid have been used for diagnosis and prognosis. Because the protein markers that are currently used in clinical tests are unreliable, proteomic studies to find new protein markers are being conducted. However, such researches have been limited due to the complexity of pancreatic cyst fluid and the immaturity of proteomic techniques.<h4>Methods</h4>To overcome these limitations and provide a pancreatic cyst proteome ...[more]

PMID: 28815810

Similar Datasets

Project description:Intraductal Papillary Mucinous Neoplasms (IPMNs) of the pancreas are cyst-like precursor lesions that give rise to 25% of pancreatic ductal adenocarcinomas (PDAC). While ~90% of cases are diagnosed before cancer forms, metrics and markers by which to determine if an IPMN will progress are currently lacking. Overall, 96% of IPMNs harbor KRAS (~80%) and/or GNAS (~66%) driver mutations and IPMN may be classified as either gastric, intestinal, or pancreatobiliary type. Recently, we identified a shared program of pyloric type metaplasia between pancreatic and gastric injury. Here, we combined immunostaining, RNA-sequencing, molecular biology, and analysis of patient samples to identify major drivers of this program in IPMN. Methods Single cell RNA-sequencing datasets of human IPMN were assayed for markers of pyloric-type metaplasia. 37 IPMN patient samples were immunostained using MxIHC for MUC5AC, CD44v9, and AQP5. KrasG12D and GnasR201C expression was modified in IPMN cell lines to identify transcriptomic programs driven by each oncogene, and in combination. Gene sets were compared to murine and human gastric cell types. Transcriptomic drivers were identified and manipulated in vitro. Candidate driver expression was evaluated by immunostaining of patient IPMN and graded. Results Analysis of published bulk and scRNA-seq IPMN datasets revealed expression of previously described markers of pyloric type metaplasia. Marker expression was confirmed in patient samples. Manipulation of KrasG12D and GnasR201C expression in IPMN cell lines identified the relative contributions of each oncogene to this gastric phenotype. Regulon analysis suggests that transcription factors SPDEF, CREB3L1, and CREB3L4 amplify this program in response to GnasR201C expression. All transcription factors were expressed in patient IPMN samples. Conclusions In response to oncogenic mutation(s), IPMN form in the pancreas and express markers of pyloric type metaplasia. KrasG12D and GnasR201C expression drive this program through independent and synergistic mechanisms that result in amplified expression of mucins and gastrokines, consistent with the phenotype identified in vivo.