Detection of candidate biomarkers of prostate cancer progression in serum: a depletion-free 3D LC/MS quantitative proteomics pilot study.
BACKGROUND
Prostate cancer (PCa) is the most common male cancer in the United Kingdom and we aimed to identify clinically relevant biomarkers corresponding to stage progression of the disease.


METHODS
We used enhanced proteomic profiling of PCa progression using iTRAQ 3D LC mass spectrometry on high-quality serum samples to identify biomarkers of PCa.


RESULTS
We identified >1000 proteins. Following specific inclusion/exclusion criteria we targeted seven proteins of which two were validated by ELISA and six potentially interacted forming an 'interactome' with only a single protein linking each marker. This network also includes accepted cancer markers, such as TNF, STAT3, NF-κB and IL6.


CONCLUSIONS
Our linked and interrelated biomarker network highlights the potential utility of six of our seven markers as a panel for diagnosing PCa and, critically, in determining the stage of the disease. Our validation analysis of the MS-identified proteins found that SAA alongside KLK3 may improve categorisation of PCa than by KLK3 alone, and that TSR1, although not significant in this model, might also be a clinically relevant biomarker.
Cancer Sciences Unit, Southampton General Hospital, University of Southampton, Southampton SO16 6YD, UK.
S E T
SE
Larkin
Cancer Sciences Unit, Southampton General Hospital, University of Southampton, Southampton SO16 6YD, UK.
H E
HE
Johnston
Institute of Cancer Sciences, Manchester Cancer Research Centre, Manchester Academic Health Science Centre, University of Manchester, Wilmslow Road, Manchester M20 4QL, UK.
T R
TR
Jackson
Biorelate, BASE, Greenhey's, Manchester Science Park, Pencroft Way, Manchester M15 6JJ, UK.
D G
DG
Jamieson
Institute for Life Sciences, Centre for Proteomic Research, University of Southampton, Southampton SO17 1BJ, UK.
T I
TI
Roumeliotis
Cancer Sciences Unit, Southampton General Hospital, University of Southampton, Southampton SO16 6YD, UK.
C I
CI
Mockridge
Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7TE, UK.
A
A
Michael
Institute for Life Sciences, Centre for Proteomic Research, University of Southampton, Southampton SO17 1BJ, UK.
A
A
Manousopoulou
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
E K
EK
Papachristou
Institute of Cancer Sciences, Cancer Research UK Manchester Institute, Paterson Building, Wilmslow Road, Manchester M20 4BX, UK.
M D
MD
Brown
The Christie NHS Foundation Trust, Manchester M20 4BX, UK.
N W
NW
Clarke
Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7TE, UK.
H
H
Pandha
Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7TE, UK.
C L
CL
Aukim-Hastie
Cancer Sciences Unit, Southampton General Hospital, University of Southampton, Southampton SO16 6YD, UK.
M S
MS
Cragg
Cancer Sciences Unit, Southampton General Hospital, University of Southampton, Southampton SO16 6YD, UK.|Institute for Life Sciences, Centre for Proteomic Research, University of Southampton, Southampton SO17 1BJ, UK.
S D
SD
Garbis
Institute of Cancer Sciences, Manchester Cancer Research Centre, Manchester Academic Health Science Centre, University of Manchester, Wilmslow Road, Manchester M20 4QL, UK.|Institute of Cancer Sciences, Cancer Research UK Manchester Institute, Paterson Building, Wilmslow Road, Manchester M20 4BX, UK.
P A
PA
Townsend
D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D001774:Blood Chemical Analysis / Q000379:methods; D002853:Chromatography, Liquid; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008297:Male; D010865:Pilot Projects; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000473:pathology*; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D014408:Biomarkers, Tumor
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