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
Hauptverfasser: 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
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container_end_page 1861
container_issue 9
container_start_page 1854
container_title British journal of cancer
container_volume 108
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
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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. 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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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