Protein shedding in urothelial bladder cancer: prognostic implications of soluble urinary EGFR and EpCAM

R T Bryan; H L Regan; S J Pirrie; A J Devall; K K Cheng; M P Zeegers; N D James; M A Knowles; D G Ward

doi:10.1038/bjc.2015.21

Protein shedding in urothelial bladder cancer: prognostic implications of soluble urinary EGFR and EpCAM

R T Bryan, H L Regan, S J Pirrie, A J Devall, K K Cheng, M P Zeegers, N D James, M A Knowles, D G Ward

Research output: Contribution to journal › Article › peer-review

28 Citations (Scopus)

180 Downloads (Pure)

Abstract

BACKGROUND: Better biomarkers must be found to develop clinically useful urine tests for bladder cancer. Proteomics can be used to identify the proteins released by cancer cell lines and generate candidate markers for developing such tests.

METHODS: We used shotgun proteomics to identify proteins released into culture media by eight bladder cancer cell lines. These data were compared with protein expression data from the Human Protein Atlas. Epidermal growth factor receptor (EGFR) was identified as a candidate biomarker and measured by ELISA in urine from 60 noncancer control subjects and from 436 patients with bladder cancer and long-term clinical follow-up.

RESULTS: Bladder cancer cell lines shed soluble EGFR ectodomain. Soluble EGFR is also detectable in urine and is highly elevated in some patients with high-grade bladder cancer. Urinary EGFR is an independent indicator of poor bladder cancer-specific survival with a hazard ratio of 2.89 (95% CI 1.81-4.62, P<0.001). In multivariable models including both urinary EGFR and EpCAM, both biomarkers are predictive of bladder cancer-specific survival and have prognostic value over and above that provided by standard clinical observations.

CONCLUSIONS: Measuring urinary EGFR and EpCAM may represent a simple and useful approach for fast-tracking the investigation and treatment of patients with the most aggressive bladder cancers.

Original language	English
Pages (from-to)	1052-8
Number of pages	7
Journal	British Journal of Cancer
Volume	112
Issue number	6
Early online date	26 Feb 2015
DOIs	https://doi.org/10.1038/bjc.2015.21
Publication status	Published - 17 Mar 2015

Keywords

Aged
Aged, 80 and over
Antigens, Neoplasm
Case-Control Studies
Cell Adhesion Molecules
Cell Line, Tumor
Female
Humans
Male
Prognosis
Receptor, Epidermal Growth Factor
Tumor Markers, Biological
Urinary Bladder Neoplasms

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/bjc.2015.21

Bryan_et_al_Protein_Shedding_BJC_2015_Post-Print
Final version of record available at: http://dx.doi.org/10.1038/bjc.2015.21 Checked October 2015
Accepted author manuscript, 348 KBLicence: None: All rights reserved

28 Citations
1 Patent

Bladder cancer prognosis
Bryan, R. & Ward, D., 2 Jun 2016, IPC No. G01N 33/574 (2006.01), G01N 33/68 (2006.01), Patent No. WO/2016/083832, Priority date 28 Nov 2014, Priority No. US 62/085,433
Research output: Patent

Open Access
File

1 Guest lecture or Invited talk

A Rough Guide to Biomarkers
Richard Bryan (Speaker)
15 Nov 2016
Activity: Academic and Industrial events › Guest lecture or Invited talk

Birmingham Environment for Academic Research (BEAR)
Facility/equipment: Equipment

Cite this

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title = "Protein shedding in urothelial bladder cancer: prognostic implications of soluble urinary EGFR and EpCAM",

abstract = "BACKGROUND: Better biomarkers must be found to develop clinically useful urine tests for bladder cancer. Proteomics can be used to identify the proteins released by cancer cell lines and generate candidate markers for developing such tests.METHODS: We used shotgun proteomics to identify proteins released into culture media by eight bladder cancer cell lines. These data were compared with protein expression data from the Human Protein Atlas. Epidermal growth factor receptor (EGFR) was identified as a candidate biomarker and measured by ELISA in urine from 60 noncancer control subjects and from 436 patients with bladder cancer and long-term clinical follow-up.RESULTS: Bladder cancer cell lines shed soluble EGFR ectodomain. Soluble EGFR is also detectable in urine and is highly elevated in some patients with high-grade bladder cancer. Urinary EGFR is an independent indicator of poor bladder cancer-specific survival with a hazard ratio of 2.89 (95% CI 1.81-4.62, P<0.001). In multivariable models including both urinary EGFR and EpCAM, both biomarkers are predictive of bladder cancer-specific survival and have prognostic value over and above that provided by standard clinical observations.CONCLUSIONS: Measuring urinary EGFR and EpCAM may represent a simple and useful approach for fast-tracking the investigation and treatment of patients with the most aggressive bladder cancers.",

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author = "Bryan, {R T} and Regan, {H L} and Pirrie, {S J} and Devall, {A J} and Cheng, {K K} and Zeegers, {M P} and James, {N D} and Knowles, {M A} and Ward, {D G}",

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AB - BACKGROUND: Better biomarkers must be found to develop clinically useful urine tests for bladder cancer. Proteomics can be used to identify the proteins released by cancer cell lines and generate candidate markers for developing such tests.METHODS: We used shotgun proteomics to identify proteins released into culture media by eight bladder cancer cell lines. These data were compared with protein expression data from the Human Protein Atlas. Epidermal growth factor receptor (EGFR) was identified as a candidate biomarker and measured by ELISA in urine from 60 noncancer control subjects and from 436 patients with bladder cancer and long-term clinical follow-up.RESULTS: Bladder cancer cell lines shed soluble EGFR ectodomain. Soluble EGFR is also detectable in urine and is highly elevated in some patients with high-grade bladder cancer. Urinary EGFR is an independent indicator of poor bladder cancer-specific survival with a hazard ratio of 2.89 (95% CI 1.81-4.62, P<0.001). In multivariable models including both urinary EGFR and EpCAM, both biomarkers are predictive of bladder cancer-specific survival and have prognostic value over and above that provided by standard clinical observations.CONCLUSIONS: Measuring urinary EGFR and EpCAM may represent a simple and useful approach for fast-tracking the investigation and treatment of patients with the most aggressive bladder cancers.

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Protein shedding in urothelial bladder cancer: prognostic implications of soluble urinary EGFR and EpCAM

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Research output

Bladder cancer prognosis

Activities

A Rough Guide to Biomarkers

Equipment

Birmingham Environment for Academic Research (BEAR)

Cite this