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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Veröffentlicht in:PloS one 2012-02, Vol.7 (2), p.e30885-e30885
Hauptverfasser: 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
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container_title PloS one
container_volume 7
creator 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
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
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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&lt;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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0030885</identifier><identifier>PMID: 22355332</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aged ; Androgens ; Antigens ; Biocompatibility ; Bioengineering ; Biological markers ; Biology ; Biomarkers ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Biomedical materials ; Blotting, Western ; Bone cancer ; Bone Neoplasms - genetics ; Bone Neoplasms - metabolism ; Bone Neoplasms - secondary ; Bones ; Cancer ; Cancer metastasis ; Cloning ; Cytokines ; Developmental stages ; Diagnosis ; Disease ; Disease Progression ; Elongation ; Health risks ; Humans ; Hyperplasia ; Identification ; Immunoenzyme Techniques ; Male ; Mass spectrometry ; Medical diagnosis ; Medical prognosis ; Medical schools ; Medicine ; Metabolism ; Metastases ; Metastasis ; Neoplasm Grading ; Osteoblasts ; Osteosarcoma - genetics ; Osteosarcoma - metabolism ; Osteosarcoma - secondary ; Panels ; Patients ; Peptide Elongation Factor 1 - genetics ; Peptide Elongation Factor 1 - metabolism ; Peptide mapping ; Prospective Studies ; Prostate cancer ; Prostate-Specific Antigen - blood ; Prostatic Hyperplasia - genetics ; Prostatic Hyperplasia - metabolism ; Prostatic Hyperplasia - pathology ; Prostatic Neoplasms - genetics ; Prostatic Neoplasms - metabolism ; Prostatic Neoplasms - pathology ; Proteins ; Proteomics ; Real-Time Polymerase Chain Reaction ; RNA, Messenger - genetics ; Scientific imaging ; Tandem Mass Spectrometry ; Translation elongation ; Tumor Cells, Cultured ; Tumors ; Urology</subject><ispartof>PloS one, 2012-02, Vol.7 (2), p.e30885-e30885</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Rehman et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Rehman et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c691t-d26d1d788d94b23e217ef951ff89fc04105801111add5e8ca3acba5dd3a4acd73</citedby><cites>FETCH-LOGICAL-c691t-d26d1d788d94b23e217ef951ff89fc04105801111add5e8ca3acba5dd3a4acd73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280251/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280251/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22355332$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Chai, Karl X.</contributor><creatorcontrib>Rehman, Ishtiaq</creatorcontrib><creatorcontrib>Evans, Caroline A</creatorcontrib><creatorcontrib>Glen, Adam</creatorcontrib><creatorcontrib>Cross, Simon S</creatorcontrib><creatorcontrib>Eaton, Colby L</creatorcontrib><creatorcontrib>Down, Jenny</creatorcontrib><creatorcontrib>Pesce, Giancarlo</creatorcontrib><creatorcontrib>Phillips, Joshua T</creatorcontrib><creatorcontrib>Yen, Ow Saw</creatorcontrib><creatorcontrib>Thalmann, George N</creatorcontrib><creatorcontrib>Wright, Phillip C</creatorcontrib><creatorcontrib>Hamdy, Freddie C</creatorcontrib><title>iTRAQ identification of candidate serum biomarkers associated with metastatic progression of human prostate cancer</title><title>PloS one</title><addtitle>PLoS One</addtitle><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&lt;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. 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risks</subject><subject>Humans</subject><subject>Hyperplasia</subject><subject>Identification</subject><subject>Immunoenzyme Techniques</subject><subject>Male</subject><subject>Mass spectrometry</subject><subject>Medical diagnosis</subject><subject>Medical prognosis</subject><subject>Medical schools</subject><subject>Medicine</subject><subject>Metabolism</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Neoplasm Grading</subject><subject>Osteoblasts</subject><subject>Osteosarcoma - genetics</subject><subject>Osteosarcoma - metabolism</subject><subject>Osteosarcoma - secondary</subject><subject>Panels</subject><subject>Patients</subject><subject>Peptide Elongation Factor 1 - genetics</subject><subject>Peptide Elongation Factor 1 - metabolism</subject><subject>Peptide mapping</subject><subject>Prospective Studies</subject><subject>Prostate cancer</subject><subject>Prostate-Specific Antigen - blood</subject><subject>Prostatic Hyperplasia - 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identification of candidate serum biomarkers associated with metastatic progression of human prostate cancer</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c691t-d26d1d788d94b23e217ef951ff89fc04105801111add5e8ca3acba5dd3a4acd73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Aged</topic><topic>Androgens</topic><topic>Antigens</topic><topic>Biocompatibility</topic><topic>Bioengineering</topic><topic>Biological markers</topic><topic>Biology</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Biomedical materials</topic><topic>Blotting, Western</topic><topic>Bone 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of human prostate cancer</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-02-15</date><risdate>2012</risdate><volume>7</volume><issue>2</issue><spage>e30885</spage><epage>e30885</epage><pages>e30885-e30885</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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&lt;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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22355332</pmid><doi>10.1371/journal.pone.0030885</doi><tpages>e30885</tpages><oa>free_for_read</oa></addata></record>
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subjects Aged
Androgens
Antigens
Biocompatibility
Bioengineering
Biological markers
Biology
Biomarkers
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Biomedical materials
Blotting, Western
Bone cancer
Bone Neoplasms - genetics
Bone Neoplasms - metabolism
Bone Neoplasms - secondary
Bones
Cancer
Cancer metastasis
Cloning
Cytokines
Developmental stages
Diagnosis
Disease
Disease Progression
Elongation
Health risks
Humans
Hyperplasia
Identification
Immunoenzyme Techniques
Male
Mass spectrometry
Medical diagnosis
Medical prognosis
Medical schools
Medicine
Metabolism
Metastases
Metastasis
Neoplasm Grading
Osteoblasts
Osteosarcoma - genetics
Osteosarcoma - metabolism
Osteosarcoma - secondary
Panels
Patients
Peptide Elongation Factor 1 - genetics
Peptide Elongation Factor 1 - metabolism
Peptide mapping
Prospective Studies
Prostate cancer
Prostate-Specific Antigen - blood
Prostatic Hyperplasia - genetics
Prostatic Hyperplasia - metabolism
Prostatic Hyperplasia - pathology
Prostatic Neoplasms - genetics
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - pathology
Proteins
Proteomics
Real-Time Polymerase Chain Reaction
RNA, Messenger - genetics
Scientific imaging
Tandem Mass Spectrometry
Translation elongation
Tumor Cells, Cultured
Tumors
Urology
title iTRAQ identification of candidate serum biomarkers associated with metastatic progression of human prostate cancer
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