Combined proteome and transcriptome analyses for the discovery of urinary biomarkers for urothelial carcinoma
Background: Proteomic discovery of cancer biomarkers in body fluids is challenging because of their low abundance in a complex background. Altered gene expression in tumours may not reflect protein levels in body fluids. We have tested combining gene expression profiling of tumours with proteomic an...
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Veröffentlicht in: | British journal of cancer 2013-05, Vol.108 (9), p.1854-1861 |
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creator | Shimwell, N J Bryan, R T Wei, W James, N D Cheng, K K Zeegers, M P Johnson, P J Martin, A Ward, D G |
description | Background:
Proteomic discovery of cancer biomarkers in body fluids is challenging because of their low abundance in a complex background. Altered gene expression in tumours may not reflect protein levels in body fluids. We have tested combining gene expression profiling of tumours with proteomic analysis of cancer cell line secretomes as a strategy to discover urinary biomarkers for bladder cancer.
Methods:
We used shotgun proteomics to identify proteins secreted by three bladder cancer cell lines. Secreted proteins with high mRNA levels in bladder tumours relative to normal urothelium were assayed by ELISA in urine samples from 642 patients.
Results:
Midkine and HAI-1 were significantly increased in bladder cancer patients, with the highest levels in invasive disease (area under the receiver operating characteristic curve 0.89
vs
non-cancer). The urinary concentration of both proteins was too high to be explained by bladder cancer associated haematuria and most likely arises by direct tumour secretion.
Conclusions:
This ‘dual-omic’ strategy identified tumour secreted proteins whose urine concentrations are increased significantly by bladder cancer. Combined secretome-transcriptome analysis may be more useful than direct proteomic analysis of body fluids for biomarker discovery in both bladder cancer and other tumour types. |
doi_str_mv | 10.1038/bjc.2013.157 |
format | Article |
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Proteomic discovery of cancer biomarkers in body fluids is challenging because of their low abundance in a complex background. Altered gene expression in tumours may not reflect protein levels in body fluids. We have tested combining gene expression profiling of tumours with proteomic analysis of cancer cell line secretomes as a strategy to discover urinary biomarkers for bladder cancer.
Methods:
We used shotgun proteomics to identify proteins secreted by three bladder cancer cell lines. Secreted proteins with high mRNA levels in bladder tumours relative to normal urothelium were assayed by ELISA in urine samples from 642 patients.
Results:
Midkine and HAI-1 were significantly increased in bladder cancer patients, with the highest levels in invasive disease (area under the receiver operating characteristic curve 0.89
vs
non-cancer). The urinary concentration of both proteins was too high to be explained by bladder cancer associated haematuria and most likely arises by direct tumour secretion.
Conclusions:
This ‘dual-omic’ strategy identified tumour secreted proteins whose urine concentrations are increased significantly by bladder cancer. Combined secretome-transcriptome analysis may be more useful than direct proteomic analysis of body fluids for biomarker discovery in both bladder cancer and other tumour types.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/bjc.2013.157</identifier><identifier>PMID: 23591195</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/45/475 ; 692/699/67/1857 ; 692/699/67/589/1336 ; Biological and medical sciences ; Biomarkers ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - urine ; Biomedical and Life Sciences ; Biomedicine ; Bladder cancer ; Body fluids ; Cancer Research ; Carcinoma, Transitional Cell - pathology ; Carcinoma, Transitional Cell - urine ; Cell Line, Tumor ; Cellular biology ; Cytokines - urine ; Drug Resistance ; Epidemiology ; Gene expression ; Gene Expression Profiling ; Hematuria ; Humans ; Medical sciences ; Molecular Diagnostics ; Molecular Medicine ; Multiple tumors. Solid tumors. Tumors in childhood (general aspects) ; Nephrology. Urinary tract diseases ; Oncology ; Protein Array Analysis ; Proteinase Inhibitory Proteins, Secretory - urine ; Proteins ; Proteinuria ; Proteome - analysis ; RNA, Messenger - analysis ; Surveillance ; Transcriptome ; Tumors ; Tumors of the urinary system ; Urinary Bladder Neoplasms - pathology ; Urinary Bladder Neoplasms - urine ; Urinary tract. Prostate gland ; Urine ; Urologic Neoplasms - pathology ; Urologic Neoplasms - urine ; Urothelium - pathology</subject><ispartof>British journal of cancer, 2013-05, Vol.108 (9), p.1854-1861</ispartof><rights>The Author(s) 2013</rights><rights>2014 INIST-CNRS</rights><rights>Copyright Nature Publishing Group May 14, 2013</rights><rights>Copyright © 2013 Cancer Research UK 2013 Cancer Research UK</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c480t-e7e4706135d4dce73a1469debd78138c1ab163fc52a988809081098aa6081e63</citedby><cites>FETCH-LOGICAL-c480t-e7e4706135d4dce73a1469debd78138c1ab163fc52a988809081098aa6081e63</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/PMC3658509/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3658509/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27922,27923,41486,42555,51317,53789,53791</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27357987$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23591195$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shimwell, N J</creatorcontrib><creatorcontrib>Bryan, R T</creatorcontrib><creatorcontrib>Wei, W</creatorcontrib><creatorcontrib>James, N D</creatorcontrib><creatorcontrib>Cheng, K K</creatorcontrib><creatorcontrib>Zeegers, M P</creatorcontrib><creatorcontrib>Johnson, P J</creatorcontrib><creatorcontrib>Martin, A</creatorcontrib><creatorcontrib>Ward, D G</creatorcontrib><title>Combined proteome and transcriptome analyses for the discovery of urinary biomarkers for urothelial carcinoma</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Background:
Proteomic discovery of cancer biomarkers in body fluids is challenging because of their low abundance in a complex background. Altered gene expression in tumours may not reflect protein levels in body fluids. We have tested combining gene expression profiling of tumours with proteomic analysis of cancer cell line secretomes as a strategy to discover urinary biomarkers for bladder cancer.
Methods:
We used shotgun proteomics to identify proteins secreted by three bladder cancer cell lines. Secreted proteins with high mRNA levels in bladder tumours relative to normal urothelium were assayed by ELISA in urine samples from 642 patients.
Results:
Midkine and HAI-1 were significantly increased in bladder cancer patients, with the highest levels in invasive disease (area under the receiver operating characteristic curve 0.89
vs
non-cancer). The urinary concentration of both proteins was too high to be explained by bladder cancer associated haematuria and most likely arises by direct tumour secretion.
Conclusions:
This ‘dual-omic’ strategy identified tumour secreted proteins whose urine concentrations are increased significantly by bladder cancer. Combined secretome-transcriptome analysis may be more useful than direct proteomic analysis of body fluids for biomarker discovery in both bladder cancer and other tumour types.</description><subject>631/45/475</subject><subject>692/699/67/1857</subject><subject>692/699/67/589/1336</subject><subject>Biological and medical sciences</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - urine</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Bladder cancer</subject><subject>Body fluids</subject><subject>Cancer Research</subject><subject>Carcinoma, Transitional Cell - pathology</subject><subject>Carcinoma, Transitional Cell - urine</subject><subject>Cell Line, Tumor</subject><subject>Cellular biology</subject><subject>Cytokines - urine</subject><subject>Drug Resistance</subject><subject>Epidemiology</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Hematuria</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Molecular Diagnostics</subject><subject>Molecular Medicine</subject><subject>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Oncology</subject><subject>Protein Array Analysis</subject><subject>Proteinase Inhibitory Proteins, Secretory - urine</subject><subject>Proteins</subject><subject>Proteinuria</subject><subject>Proteome - analysis</subject><subject>RNA, Messenger - analysis</subject><subject>Surveillance</subject><subject>Transcriptome</subject><subject>Tumors</subject><subject>Tumors of the urinary system</subject><subject>Urinary Bladder Neoplasms - pathology</subject><subject>Urinary Bladder Neoplasms - urine</subject><subject>Urinary tract. Prostate gland</subject><subject>Urine</subject><subject>Urologic Neoplasms - pathology</subject><subject>Urologic Neoplasms - urine</subject><subject>Urothelium - pathology</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNptkUtr3DAUhUVpaKZpd10XQyl0UU8ky7KkTaAMfUEgm-yFLF9nNLWlqWQH5t_3Tj1J09KVHvfj6BwdQt4wumaUq8t259YVZXzNhHxGVkzwqmSqks_JilIqS6orek5e5rzDo6ZKviDnFReaMS1WZNzEsfUBumKf4gRxhMKGrpiSDdklv5-WGzscMuSij6mYtlB0Prt4D-lQxL6Ykw8Wt62Po00_IC3cjHpbGLwdCmeT8wGnr8hZb4cMr0_rBbn98vl28628vvn6ffPpunS1olMJEmpJG8ZFV3cOJLesbnQHbScV48ox27KG905UViuljqkY1craBjfQ8Atytcju53YEVAiYZzD75NHgwUTrzd-T4LfmLt4b3gglqEaBDyeBFH_OkCczYmIYBhsgztmgs6qSSkiJ6Lt_0F2cE37Yb4pqJquaIfVxoVyKOSfoH80wao41GqzRHGs0WCPib58GeIQfekPg_Qmw2dmhx7qcz384yYXU6ihULlzGUbiD9MTd_x7-BfIgtlo</recordid><startdate>20130514</startdate><enddate>20130514</enddate><creator>Shimwell, N J</creator><creator>Bryan, R T</creator><creator>Wei, W</creator><creator>James, N D</creator><creator>Cheng, K K</creator><creator>Zeegers, M P</creator><creator>Johnson, P J</creator><creator>Martin, A</creator><creator>Ward, D G</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20130514</creationdate><title>Combined proteome and transcriptome analyses for the discovery of urinary biomarkers for urothelial carcinoma</title><author>Shimwell, N J ; Bryan, R T ; Wei, W ; James, N D ; Cheng, K K ; Zeegers, M P ; Johnson, P J ; Martin, A ; Ward, D G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c480t-e7e4706135d4dce73a1469debd78138c1ab163fc52a988809081098aa6081e63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>631/45/475</topic><topic>692/699/67/1857</topic><topic>692/699/67/589/1336</topic><topic>Biological and medical sciences</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - urine</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Bladder cancer</topic><topic>Body fluids</topic><topic>Cancer Research</topic><topic>Carcinoma, Transitional Cell - pathology</topic><topic>Carcinoma, Transitional Cell - urine</topic><topic>Cell Line, Tumor</topic><topic>Cellular biology</topic><topic>Cytokines - urine</topic><topic>Drug Resistance</topic><topic>Epidemiology</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Hematuria</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Molecular Diagnostics</topic><topic>Molecular Medicine</topic><topic>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Oncology</topic><topic>Protein Array Analysis</topic><topic>Proteinase Inhibitory Proteins, Secretory - urine</topic><topic>Proteins</topic><topic>Proteinuria</topic><topic>Proteome - analysis</topic><topic>RNA, Messenger - analysis</topic><topic>Surveillance</topic><topic>Transcriptome</topic><topic>Tumors</topic><topic>Tumors of the urinary system</topic><topic>Urinary Bladder Neoplasms - pathology</topic><topic>Urinary Bladder Neoplasms - urine</topic><topic>Urinary tract. Prostate gland</topic><topic>Urine</topic><topic>Urologic Neoplasms - pathology</topic><topic>Urologic Neoplasms - urine</topic><topic>Urothelium - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shimwell, N J</creatorcontrib><creatorcontrib>Bryan, R T</creatorcontrib><creatorcontrib>Wei, W</creatorcontrib><creatorcontrib>James, N D</creatorcontrib><creatorcontrib>Cheng, K K</creatorcontrib><creatorcontrib>Zeegers, M P</creatorcontrib><creatorcontrib>Johnson, P J</creatorcontrib><creatorcontrib>Martin, A</creatorcontrib><creatorcontrib>Ward, D G</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shimwell, N J</au><au>Bryan, R T</au><au>Wei, W</au><au>James, N D</au><au>Cheng, K K</au><au>Zeegers, M P</au><au>Johnson, P J</au><au>Martin, A</au><au>Ward, D G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Combined proteome and transcriptome analyses for the discovery of urinary biomarkers for urothelial carcinoma</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2013-05-14</date><risdate>2013</risdate><volume>108</volume><issue>9</issue><spage>1854</spage><epage>1861</epage><pages>1854-1861</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><coden>BJCAAI</coden><abstract>Background:
Proteomic discovery of cancer biomarkers in body fluids is challenging because of their low abundance in a complex background. Altered gene expression in tumours may not reflect protein levels in body fluids. We have tested combining gene expression profiling of tumours with proteomic analysis of cancer cell line secretomes as a strategy to discover urinary biomarkers for bladder cancer.
Methods:
We used shotgun proteomics to identify proteins secreted by three bladder cancer cell lines. Secreted proteins with high mRNA levels in bladder tumours relative to normal urothelium were assayed by ELISA in urine samples from 642 patients.
Results:
Midkine and HAI-1 were significantly increased in bladder cancer patients, with the highest levels in invasive disease (area under the receiver operating characteristic curve 0.89
vs
non-cancer). The urinary concentration of both proteins was too high to be explained by bladder cancer associated haematuria and most likely arises by direct tumour secretion.
Conclusions:
This ‘dual-omic’ strategy identified tumour secreted proteins whose urine concentrations are increased significantly by bladder cancer. Combined secretome-transcriptome analysis may be more useful than direct proteomic analysis of body fluids for biomarker discovery in both bladder cancer and other tumour types.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>23591195</pmid><doi>10.1038/bjc.2013.157</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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subjects | 631/45/475 692/699/67/1857 692/699/67/589/1336 Biological and medical sciences Biomarkers Biomarkers, Tumor - genetics Biomarkers, Tumor - urine Biomedical and Life Sciences Biomedicine Bladder cancer Body fluids Cancer Research Carcinoma, Transitional Cell - pathology Carcinoma, Transitional Cell - urine Cell Line, Tumor Cellular biology Cytokines - urine Drug Resistance Epidemiology Gene expression Gene Expression Profiling Hematuria Humans Medical sciences Molecular Diagnostics Molecular Medicine Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Nephrology. Urinary tract diseases Oncology Protein Array Analysis Proteinase Inhibitory Proteins, Secretory - urine Proteins Proteinuria Proteome - analysis RNA, Messenger - analysis Surveillance Transcriptome Tumors Tumors of the urinary system Urinary Bladder Neoplasms - pathology Urinary Bladder Neoplasms - urine Urinary tract. Prostate gland Urine Urologic Neoplasms - pathology Urologic Neoplasms - urine Urothelium - pathology |
title | Combined proteome and transcriptome analyses for the discovery of urinary biomarkers for urothelial carcinoma |
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