Metabolites of purine nucleoside Phosphorylase (NP) in serum have the potential to delineate Pancreatic Adenocarcinoma

Shaiju K. Vareed, Vadiraja B. Bhat, Christopher Thompson, Vihas T. Vasu, Damian Fermin, Hyungwon Choi, Chad J. Creighton, Sitaram Gayatri, Ling Lan, Nagireddy Putluri, Gagan Singh Thangjam, Punit Kaur, Mohsen Shabahang, Judith G. Giri, Alexey I. Nesvizhskii, Alexander A.A. Asea, Anil G. Cashikar, Arundhati Rao, James Mcloughlin, Arun Sreekumar

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article numbere17177
JournalPloS one
Volume6
Issue number3
DOIs
StatePublished - Mar 28 2011

Fingerprint

Purine-Nucleoside Phosphorylase
alpha-Synuclein
phosphorylase
nucleosides
purines
Metabolites
adenocarcinoma
Adenocarcinoma
metabolites
Biomarkers
Serum
neoplasms
Parkinson disease
Tumors
Neoplasms
Tissue Array Analysis
Tissue
Staining and Labeling
biomarkers
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Vareed, S. K., Bhat, V. B., Thompson, C., Vasu, V. T., Fermin, D., Choi, H., ... Sreekumar, A. (2011). Metabolites of purine nucleoside Phosphorylase (NP) in serum have the potential to delineate Pancreatic Adenocarcinoma. PloS one, 6(3), [e17177]. https://doi.org/10.1371/journal.pone.0017177

Metabolites of purine nucleoside Phosphorylase (NP) in serum have the potential to delineate Pancreatic Adenocarcinoma. / 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.; Cashikar, Anil G.; Rao, Arundhati; Mcloughlin, James; Sreekumar, Arun.

In: PloS one, Vol. 6, No. 3, e17177, 28.03.2011.

Research output: Contribution to journalArticle

Vareed, SK, Bhat, VB, Thompson, C, Vasu, VT, Fermin, D, Choi, H, Creighton, CJ, Gayatri, S, Lan, L, Putluri, N, Thangjam, GS, Kaur, P, Shabahang, M, Giri, JG, Nesvizhskii, AI, Asea, AAA, Cashikar, AG, Rao, A, Mcloughlin, J & Sreekumar, A 2011, 'Metabolites of purine nucleoside Phosphorylase (NP) in serum have the potential to delineate Pancreatic Adenocarcinoma', PloS one, vol. 6, no. 3, e17177. https://doi.org/10.1371/journal.pone.0017177
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. ; Cashikar, Anil G. ; Rao, Arundhati ; Mcloughlin, James ; Sreekumar, Arun. / Metabolites of purine nucleoside Phosphorylase (NP) in serum have the potential to delineate Pancreatic Adenocarcinoma. In: PloS one. 2011 ; Vol. 6, No. 3.
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AU - Vareed, Shaiju K.

AU - Bhat, Vadiraja B.

AU - Thompson, Christopher

AU - Vasu, Vihas T.

AU - Fermin, Damian

AU - Choi, Hyungwon

AU - Creighton, Chad J.

AU - Gayatri, Sitaram

AU - Lan, Ling

AU - Putluri, Nagireddy

AU - Thangjam, Gagan Singh

AU - Kaur, Punit

AU - Shabahang, Mohsen

AU - Giri, Judith G.

AU - Nesvizhskii, Alexey I.

AU - Asea, Alexander A.A.

AU - Cashikar, Anil G.

AU - Rao, Arundhati

AU - Mcloughlin, James

AU - Sreekumar, Arun

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