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

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...

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Autores principales: Ishtiaq Rehman, Caroline A Evans, Adam Glen, Simon S Cross, Colby L Eaton, Jenny Down, Giancarlo Pesce, Joshua T Phillips, Ow Saw Yen, George N Thalmann, Phillip C Wright, Freddie C Hamdy
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:7a4c7d04ad2d482c8657cbddab3a930d2021-11-18T07:28:14ZiTRAQ identification of candidate serum biomarkers associated with metastatic progression of human prostate cancer.1932-620310.1371/journal.pone.0030885https://doaj.org/article/7a4c7d04ad2d482c8657cbddab3a930d2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22355332/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203A 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.Ishtiaq RehmanCaroline A EvansAdam GlenSimon S CrossColby L EatonJenny DownGiancarlo PesceJoshua T PhillipsOw Saw YenGeorge N ThalmannPhillip C WrightFreddie C HamdyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 2, p e30885 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Ishtiaq Rehman
Caroline A Evans
Adam Glen
Simon S Cross
Colby L Eaton
Jenny Down
Giancarlo Pesce
Joshua T Phillips
Ow Saw Yen
George N Thalmann
Phillip C Wright
Freddie C Hamdy
iTRAQ identification of candidate serum biomarkers associated with metastatic progression of human prostate cancer.
description 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.
format article
author Ishtiaq Rehman
Caroline A Evans
Adam Glen
Simon S Cross
Colby L Eaton
Jenny Down
Giancarlo Pesce
Joshua T Phillips
Ow Saw Yen
George N Thalmann
Phillip C Wright
Freddie C Hamdy
author_facet Ishtiaq Rehman
Caroline A Evans
Adam Glen
Simon S Cross
Colby L Eaton
Jenny Down
Giancarlo Pesce
Joshua T Phillips
Ow Saw Yen
George N Thalmann
Phillip C Wright
Freddie C Hamdy
author_sort Ishtiaq Rehman
title iTRAQ identification of candidate serum biomarkers associated with metastatic progression of human prostate cancer.
title_short iTRAQ identification of candidate serum biomarkers associated with metastatic progression of human prostate cancer.
title_full iTRAQ identification of candidate serum biomarkers associated with metastatic progression of human prostate cancer.
title_fullStr iTRAQ identification of candidate serum biomarkers associated with metastatic progression of human prostate cancer.
title_full_unstemmed iTRAQ identification of candidate serum biomarkers associated with metastatic progression of human prostate cancer.
title_sort itraq identification of candidate serum biomarkers associated with metastatic progression of human prostate cancer.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/7a4c7d04ad2d482c8657cbddab3a930d
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