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Proteomic analysis of ovarian cancer proximal fluids: Validation of elevated peroxiredoxin 1 in patient peripheral circulation

Hoskins, ER and Hood, BL and Sun, M and Krivak, TC and Edwards, RP and Conrads, TP (2011) Proteomic analysis of ovarian cancer proximal fluids: Validation of elevated peroxiredoxin 1 in patient peripheral circulation. PLoS ONE, 6 (9).

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Abstract

Background: Epithelial ovarian cancer (EOC) is the deadliest gynecologic malignancy in the United States. Unfortunately, a validated protein biomarker-screening test to detect early stage disease from peripheral blood has not yet been developed. The present investigation assesses the ability to identify tumor relevant proteins from ovarian cancer proximal fluids, including tissue interstitial fluid (TIF) and corresponding ascites, from patients with papillary serous EOC and translates these findings to targeted blood-based immunoassays. Methodology/Principal Findings: Paired TIF and ascites collected from four papillary serous EOC patients at the time of surgery underwent immunodepletion, resolution by 1D gel electrophoresis and in-gel digestion for analysis by liquid chromatography-tandem mass spectrometry, which resulted in an aggregate identification of 569 and 171 proteins from TIF and ascites, respectively. Of these, peroxiredoxin I (PRDX1) was selected for validation in serum by ELISA and demonstrated to be present and significantly elevated (p = 0.0188) in 20 EOC patients with a mean level of 26.0 ng/mL (±9.27 SEM) as compared to 4.19 ng/mL (±2.58 SEM) from 16 patients with normal/benign ovarian pathology. Conclusions/Significance: We have utilized a workflow for harvesting EOC-relevant proximal biofluids, including TIF and ascites, for proteomic analysis. Among the differentially abundant proteins identified from these proximal fluids, PRDX1 was demonstrated to be present in serum and shown by ELISA to be elevated by nearly 6-fold in papillary serous EOC patients relative to normal/benign patients. Our findings demonstrate the facile ability to discover potential EOC-relevant proteins in proximal fluids and confirm their presence in peripheral blood serum. In addition, our finding of elevated levels of PRDX1 in the serum of EOC patients versus normal/benign patients warrants further evaluation as a tumor specific biomarker for EOC. © 2011 Hoskins et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Hoskins, ER
Hood, BL
Sun, Mmas197@pitt.eduMAS197
Krivak, TC
Edwards, RPrpe1@pitt.eduRPE10000-0003-0370-1390
Conrads, TP
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorBatra, S. K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, Offices, or Units > Pittsburgh Cancer Institute
Date: 30 September 2011
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 6
Number: 9
DOI or Unique Handle: 10.1371/journal.pone.0025056
Schools and Programs: School of Medicine > Obstetrics, Gynecology, and Reproductive Sciences
Refereed: Yes
MeSH Headings: Adult; Aged; Blotting, Western; Chromatography, Liquid; Extracellular Fluid--metabolism; Female; Humans; Middle Aged; Neoplasms, Glandular and Epithelial--metabolism; Ovarian Neoplasms--metabolism; Peroxiredoxins--metabolism; Proteomics--methods; Tandem Mass Spectrometry
Other ID: NLM PMC3184097
PubMed Central ID: PMC3184097
PubMed ID: 21980378
Date Deposited: 05 Sep 2012 20:08
Last Modified: 29 Jan 2019 15:55
URI: http://d-scholarship.pitt.edu/id/eprint/13902

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