title: Metabolites of purine nucleoside phosphorylase (NP) in serum have the potential to delineate pancreatic adenocarcinoma.
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.
authors: Department of Biochemistry and Molecular Biology and Cancer Center, Medical College of Georgia, Augusta, Georgia, United States of America.
authors: Shaiju K
authors: SK
authors: Vareed
authors: Vadiraja B
authors: VB
authors: Bhat
authors: Christopher
authors: C
authors: Thompson
authors: Vihas T
authors: VT
authors: Vasu
authors: Damian
authors: D
authors: Fermin
authors: Hyungwon
authors: H
authors: Choi
authors: Chad J
authors: CJ
authors: Creighton
authors: Sitaram
authors: S
authors: Gayatri
authors: Ling
authors: L
authors: Lan
authors: Nagireddy
authors: N
authors: Putluri
authors: Gagan Singh
authors: GS
authors: Thangjam
authors: Punit
authors: P
authors: Kaur
authors: Mohsen
authors: M
authors: Shabahang
authors: Judith G
authors: JG
authors: Giri
authors: Alexey I
authors: AI
authors: Nesvizhskii
authors: Alexander A A
authors: AA
authors: Asea
authors: Anil G
authors: AG
authors: Cashikar
authors: Arundhati
authors: A
authors: Rao
authors: James
authors: J
authors: McLoughlin
authors: Arun
authors: A
authors: Sreekumar
mesh_terms: D015415:Biomarkers / Q000097:blood; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000201:enzymology*; D020543:Proteome / Q000378:metabolism; D040901:Proteomics; D011683:Purine-Nucleoside Phosphorylase / Q000097:blood* / Q000378:metabolism*; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers; D009363:Neoplasm Proteins; D020543:Proteome; D011683:Purine-Nucleoside Phosphorylase