Research Papers:

Exploring the roles of urinary HAI-1, EpCAM & EGFR in bladder cancer prognosis & risk stratification

Kym I.E. Snell, Douglas G. Ward, Naheema S. Gordon, James C. Goldsmith, Andrew J. Sutton, Prashant Patel, Nicholas D. James, Maurice P. Zeegers, K.K. Cheng and Richard T. Bryan _

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Oncotarget. 2018; 9:25244-25253. https://doi.org/10.18632/oncotarget.25397

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Kym I.E. Snell1, Douglas G. Ward2, Naheema S. Gordon2, James C. Goldsmith2, Andrew J. Sutton3, Prashant Patel4, Nicholas D. James2, Maurice P. Zeegers5, K.K. Cheng6 and Richard T. Bryan2

1Centre for Prognosis Research, Research Institute for Primary Care and Health Science, Keele University, Newcastle-under-Lyme, ST5 5BG, UK

2Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham B15 2TT, UK

3Leeds Institute of Health Sciences, University of Leeds and The Diagnostic Evidence Cooperative, Leeds LS2 9JT, UK

4Institute of Cancer and Genomic Sciences, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2TH, UK

5NUTRIM School for Nutrition and Translational Research in Metabolism and CAPHRI Care and Public Health Research Institute, Maastricht University, Maastricht 6200 MD, The Netherlands

6Institute of Applied Health Research, University of Birmingham, Birmingham B15 2TT, UK

Correspondence to:

Richard T. Bryan, email: [email protected]

Keywords: HAI-1; EpCAM; EGFR; bladder cancer; prognosis

Received: February 16, 2018     Accepted: April 28, 2018     Published: May 18, 2018


Objectives: To investigate whether elevated urinary HAI-1, EpCAM and EGFR are independent prognostic biomarkers within non-muscle-invasive bladder cancer (NMIBC) patients, and have utility for risk stratification to facilitate treatment decisions.

Results: After accounting for EAU risk group in NMIBC patients, the risk of BC-specific death was 2.14 times higher (95% CI: 1.08 to 4.24) if HAI-1 was elevated and 2.04 times higher (95% CI: 1.02 to 4.07) if EpCAM was elevated. The majority of events occurred in the high-risk NMIBC group and this is where the biggest difference is seen in the survival curves when plotted for EAU risk groups separately. In MIBC patients, being elevated for any of the three biomarkers was significantly associated with BC-specific mortality after accounting for other risk factors, HR = 4.30 (95% CI: 1.85 to 10.03).

Patients and Methods: Urinary levels of HAI-1, EpCAM and EGFR were measured by ELISA in 683 and 175 patients with newly-diagnosed NMIBC and MIBC, respectively, recruited to the Bladder Cancer Prognosis Programme. Associations between biomarkers and progression, BC-specific mortality and all-cause mortality were evaluated using univariable and multivariable Cox regression models, adjusted for European Association of Urology (EAU) NMIBC risk groups. The upper 25% of values for each biomarker within NMIBC patients were considered as elevated. Exploratory analyses in urine from MIBC patients were also undertaken.

Conclusion: Urinary HAI-1 and EpCAM are prognostic biomarkers for NMIBC patients. These biomarkers have potential to guide treatment decisions for high-risk NMIBC patients. Further analyses are required to define the roles of HAI-1, EpCAM and EGFR in MIBC patients.

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