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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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<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<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><subject>Aged</subject><subject>Androgens</subject><subject>Antigens</subject><subject>Biocompatibility</subject><subject>Bioengineering</subject><subject>Biological markers</subject><subject>Biology</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Biomedical materials</subject><subject>Blotting, Western</subject><subject>Bone cancer</subject><subject>Bone Neoplasms - genetics</subject><subject>Bone Neoplasms - metabolism</subject><subject>Bone Neoplasms - secondary</subject><subject>Bones</subject><subject>Cancer</subject><subject>Cancer metastasis</subject><subject>Cloning</subject><subject>Cytokines</subject><subject>Developmental stages</subject><subject>Diagnosis</subject><subject>Disease</subject><subject>Disease Progression</subject><subject>Elongation</subject><subject>Health 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 - genetics</subject><subject>Prostatic Hyperplasia - metabolism</subject><subject>Prostatic Hyperplasia - pathology</subject><subject>Prostatic Neoplasms - genetics</subject><subject>Prostatic Neoplasms - metabolism</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Proteins</subject><subject>Proteomics</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>RNA, Messenger - genetics</subject><subject>Scientific imaging</subject><subject>Tandem Mass Spectrometry</subject><subject>Translation elongation</subject><subject>Tumor Cells, 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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<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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identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2012-02, Vol.7 (2), p.e30885-e30885 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_1332949097 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
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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