Metabolites of Purine Nucleoside Phosphorylase (NP) in Serum Have the Potential to Delineate Pancreatic Adenocarcinoma

Hdl Handle:
http://hdl.handle.net/10675.2/642
Title:
Metabolites of Purine Nucleoside Phosphorylase (NP) in Serum Have the Potential to Delineate Pancreatic Adenocarcinoma
Authors:
Vareed, Shaiju K.; Bhat, Vadiraja B.; Thompson, Christopher; Vasu, Vihas T.; Fermin, Damian; Choi, Hyungwon; Creighton, Chad J.; Gayatri, Sitaram; Lan, Ling; Putluri, Nagireddy; Thangjam, Gagan Singh; Kaur, Punit; Shabahang, Mohsen; Giri, Judith G.; Nesvizhskii, Alexey I.; Asea, Alexander A. A. ( 0000-0003-3592-3481 ) ; Cashikar, Anil G.; Rao, Arundhati; McLoughlin, James; Sreekumar, Arun
Abstract:
Pancreatic Adenocarcinoma (PDAC), the fourth highest cause of cancer related deaths in the United States, has the most aggressive presentation resulting in a very short median survival time for the affected patients. Early detection of PDAC is confounded by lack of specific markers that has motivated the use of high throughput molecular approaches to delineate potential biomarkers. To pursue identification of a distinct marker, this study profiled the secretory proteome in 16 PDAC, 2 carcinoma in situ (CIS) and 7 benign patients using label-free mass spectrometry coupled to 1D-SDS-PAGE and Strong Cation-Exchange Chromatography (SCX). A total of 431 proteins were detected of which 56 were found to be significantly elevated in PDAC. Included in this differential set were Parkinson disease autosomal recessive, early onset 7 (PARK 7) and Alpha Synuclein (aSyn), both of which are known to be pathognomonic to Parkinson's disease as well as metabolic enzymes like Purine Nucleoside Phosphorylase (NP) which has been exploited as therapeutic target in cancers. Tissue Microarray analysis confirmed higher expression of aSyn and NP in ductal epithelia of pancreatic tumors compared to benign ducts. Furthermore, extent of both aSyn and NP staining positively correlated with tumor stage and perineural invasion while their intensity of staining correlated with the existence of metastatic lesions in the PDAC tissues. From the biomarker perspective, NP protein levels were higher in PDAC sera and furthermore serum levels of its downstream metabolites guanosine and adenosine were able to distinguish PDAC from benign in an unsupervised hierarchical classification model. Overall, this study for the first time describes elevated levels of aSyn in PDAC as well as highlights the potential of evaluating NP protein expression and levels of its downstream metabolites to develop a multiplex panel for non-invasive detection of PDAC.
Citation:
PLoS One. 2011 Mar 23; 6(3):e17177
Issue Date:
23-Mar-2011
URI:
http://hdl.handle.net/10675.2/642
DOI:
10.1371/journal.pone.0017177
PubMed ID:
21448452
PubMed Central ID:
PMC3063153
Type:
Article
ISSN:
1932-6203
Appears in Collections:
Department of Biochemistry and Molecular Biology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorVareed, Shaiju K.en_US
dc.contributor.authorBhat, Vadiraja B.en_US
dc.contributor.authorThompson, Christopheren_US
dc.contributor.authorVasu, Vihas T.en_US
dc.contributor.authorFermin, Damianen_US
dc.contributor.authorChoi, Hyungwonen_US
dc.contributor.authorCreighton, Chad J.en_US
dc.contributor.authorGayatri, Sitaramen_US
dc.contributor.authorLan, Lingen_US
dc.contributor.authorPutluri, Nagireddyen_US
dc.contributor.authorThangjam, Gagan Singhen_US
dc.contributor.authorKaur, Puniten_US
dc.contributor.authorShabahang, Mohsenen_US
dc.contributor.authorGiri, Judith G.en_US
dc.contributor.authorNesvizhskii, Alexey I.en_US
dc.contributor.authorAsea, Alexander A. A.en_US
dc.contributor.authorCashikar, Anil G.en_US
dc.contributor.authorRao, Arundhatien_US
dc.contributor.authorMcLoughlin, Jamesen_US
dc.contributor.authorSreekumar, Arunen_US
dc.date.accessioned2012-10-26T16:26:58Z-
dc.date.available2012-10-26T16:26:58Z-
dc.date.issued2011-03-23en_US
dc.identifier.citationPLoS One. 2011 Mar 23; 6(3):e17177en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid21448452en_US
dc.identifier.doi10.1371/journal.pone.0017177en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/642-
dc.description.abstractPancreatic Adenocarcinoma (PDAC), the fourth highest cause of cancer related deaths in the United States, has the most aggressive presentation resulting in a very short median survival time for the affected patients. Early detection of PDAC is confounded by lack of specific markers that has motivated the use of high throughput molecular approaches to delineate potential biomarkers. To pursue identification of a distinct marker, this study profiled the secretory proteome in 16 PDAC, 2 carcinoma in situ (CIS) and 7 benign patients using label-free mass spectrometry coupled to 1D-SDS-PAGE and Strong Cation-Exchange Chromatography (SCX). A total of 431 proteins were detected of which 56 were found to be significantly elevated in PDAC. Included in this differential set were Parkinson disease autosomal recessive, early onset 7 (PARK 7) and Alpha Synuclein (aSyn), both of which are known to be pathognomonic to Parkinson's disease as well as metabolic enzymes like Purine Nucleoside Phosphorylase (NP) which has been exploited as therapeutic target in cancers. Tissue Microarray analysis confirmed higher expression of aSyn and NP in ductal epithelia of pancreatic tumors compared to benign ducts. Furthermore, extent of both aSyn and NP staining positively correlated with tumor stage and perineural invasion while their intensity of staining correlated with the existence of metastatic lesions in the PDAC tissues. From the biomarker perspective, NP protein levels were higher in PDAC sera and furthermore serum levels of its downstream metabolites guanosine and adenosine were able to distinguish PDAC from benign in an unsupervised hierarchical classification model. Overall, this study for the first time describes elevated levels of aSyn in PDAC as well as highlights the potential of evaluating NP protein expression and levels of its downstream metabolites to develop a multiplex panel for non-invasive detection of PDAC.en_US
dc.rightsVareed et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectResearch Articleen_US
dc.subjectBiologyen_US
dc.subjectProteomicsen_US
dc.subjectMedicineen_US
dc.subjectDiagnostic Medicineen_US
dc.subjectPathologyen_US
dc.subjectGeneral Pathologyen_US
dc.subjectBiomarkersen_US
dc.subjectOncologyen_US
dc.subjectCancer Detection and Diagnosisen_US
dc.subjectEarly Detectionen_US
dc.subjectCancers and Neoplasmsen_US
dc.subjectGastrointestinal Tumorsen_US
dc.subjectPancreatic Canceren_US
dc.titleMetabolites of Purine Nucleoside Phosphorylase (NP) in Serum Have the Potential to Delineate Pancreatic Adenocarcinomaen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3063153en_US
dc.contributor.corporatenameDepartment of Biochemistry and Molecular Biology-
dc.contributor.corporatenameGHSU Cancer Center-
dc.contributor.corporatenameCenter for Molecular Chaperone/Radiobiology & Cancer Virology-
dc.contributor.corporatenameDepartment of Biostatistics and Epidemiology-
dc.contributor.corporatenameTumor Bank, Department of Pathology-

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