iTRAQ identification of candidate serum biomarkers associated with metastatic progression of human prostate cancer

Rehman, Ishtiaq; Evans, Caroline A.; Glen, Adam; Cross, Simon S.; Eaton, Colby L.; Down, Jenny; Pesce, Giancarlo; Phillips, Joshua T.; Yen, Ow Saw; Thalmann, George N.; Wright, Phillip C.; Hamdy, Freddie C. (2012). iTRAQ identification of candidate serum biomarkers associated with metastatic progression of human prostate cancer. PLoS ONE, 7(2), e30885. Lawrence, Kans.: Public Library of Science 10.1371/journal.pone.0030885

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A major challenge in the management of patients with prostate cancer is identifying those individuals at risk of developing metastatic disease, as in most cases the disease will remain indolent. We analyzed pooled serum samples from 4 groups of patients (n = 5 samples/group), collected prospectively and actively monitored for a minimum of 5 yrs. Patients groups were (i) histological diagnosis of benign prostatic hyperplasia with no evidence of cancer 'BPH', (ii) localised cancer with no evidence of progression, 'non-progressing' (iii) localised cancer with evidence of biochemical progression, 'progressing', and (iv) bone metastasis at presentation 'metastatic'. Pooled samples were immuno-depleted of the 14 most highly abundant proteins and analysed using a 4-plex iTRAQ approach. Overall 122 proteins were identified and relatively quantified. Comparisons of progressing versus non-progressing groups identified the significant differential expression of 25 proteins (p<0.001). Comparisons of metastatic versus progressing groups identified the significant differential expression of 23 proteins. Mapping the differentially expressed proteins onto the prostate cancer progression pathway revealed the dysregulated expression of individual proteins, pairs of proteins and 'panels' of proteins to be associated with particular stages of disease development and progression. The median immunostaining intensity of eukaryotic translation elongation factor 1 alpha 1 (eEF1A1), one of the candidates identified, was significantly higher in osteoblasts in close proximity to metastatic tumour cells compared with osteoblasts in control bone (p = 0.0353, Mann Whitney U). Our proteomic approach has identified leads for potentially useful serum biomarkers associated with the metastatic progression of prostate cancer. The panels identified, including eEF1A1 warrant further investigation and validation.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology

UniBE Contributor:

Thalmann, George

ISSN:

1932-6203

Publisher:

Public Library of Science

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:38

Last Modified:

30 Dec 2014 09:18

Publisher DOI:

10.1371/journal.pone.0030885

PubMed ID:

22355332

Web of Science ID:

000302741300032

BORIS DOI:

10.7892/boris.15438

URI:

https://boris.unibe.ch/id/eprint/15438 (FactScience: 222783)

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