Hypoxia marker GLUT-1 (glucose transporter 1) is an independent prognostic factor for survival in bladder cancer patients treated with radical cystectomy

P. J. Boström; J. Thoms; J. Sykes; O. Ahmed; A. Evans; B. W.G. Van Rhijn; T. Mirtti; O. Stakhovskyi; M. Laato; D. Margel; M. Pintilie; C. Kuk; M. Milosevic; A. R. Zlotta; R. G. Bristow

doi:10.3233/BLC-150033

Hypoxia marker GLUT-1 (glucose transporter 1) is an independent prognostic factor for survival in bladder cancer patients treated with radical cystectomy

P. J. Boström, J. Thoms, J. Sykes, O. Ahmed, A. Evans, B. W.G. Van Rhijn, T. Mirtti, O. Stakhovskyi, M. Laato, D. Margel, M. Pintilie, C. Kuk, M. Milosevic, A. R. Zlotta, R. G. Bristow

Division of Cancer Sciences (L5)

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

Abstract

Background: Tumour hypoxia, which is frequent in many cancer types, is associated with treatment resistance and poor prognosis. The role of hypoxia in surgically treated bladder cancer (BC) is not well described. We studied the role of hypoxia in two independent series of urothelial bladder cancers treated with radical cystectomy. Methods: 279 patients from the University Hospital Network (UHN), Toronto, Canada, and Turku University, Finland were studied. Hypoxia biomarkers (HIF1, CAIX, GLUT-1) and proliferation marker Ki-67 were analyzed with immunohistochemistry using defined tissue microarrays. Kaplan-Meier methods and Cox proportional hazards regression models were used to investigate prognostic role of the factors. Results: In univariate analyses, strong GLUT-1 positivity and a high Ki-67 index were associated with poor survival. In multivariate model containing clinical prognostic variables, GLUT-1 was an independent prognostic factor associated with worse disease-specific survival (HR 2.9, 95%CI 0.7-12.6,Wald p = 0.15 in the Toronto cohort and HR 3.2, 95%CI 1.3-7.5,Wald p = 0.0085 in the Turku cohort). Conclusion: GLUT-1 is frequently upregulated and is an independent prognostic factor in surgically treated bladder cancer. Further studies are needed to evaluate the potential role of hypoxia-based and targeted therapies in hypoxic bladder tumours.

Original language	English
Pages (from-to)	101-109
Number of pages	9
Journal	Bladder Cancer
Volume	2
Issue number	1
DOIs	https://doi.org/10.3233/BLC-150033
Publication status	Published - 1 Jan 2016

Keywords

Bladder cancer
CAIX
GLUT-1
HIF1α
Hypoxia

Research Beacons, Institutes and Platforms

Manchester Cancer Research Centre

UN SDGs

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

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10.3233/BLC-150033

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Boström, P. J., Thoms, J., Sykes, J., Ahmed, O., Evans, A., Van Rhijn, B. W. G., Mirtti, T., Stakhovskyi, O., Laato, M., Margel, D., Pintilie, M., Kuk, C., Milosevic, M., Zlotta, A. R., & Bristow, R. G. (2016). Hypoxia marker GLUT-1 (glucose transporter 1) is an independent prognostic factor for survival in bladder cancer patients treated with radical cystectomy. Bladder Cancer, 2(1), 101-109. https://doi.org/10.3233/BLC-150033

@article{ecf5dd6c3e4545f9b81c0d936d80c73a,

title = "Hypoxia marker GLUT-1 (glucose transporter 1) is an independent prognostic factor for survival in bladder cancer patients treated with radical cystectomy",

abstract = "Background: Tumour hypoxia, which is frequent in many cancer types, is associated with treatment resistance and poor prognosis. The role of hypoxia in surgically treated bladder cancer (BC) is not well described. We studied the role of hypoxia in two independent series of urothelial bladder cancers treated with radical cystectomy. Methods: 279 patients from the University Hospital Network (UHN), Toronto, Canada, and Turku University, Finland were studied. Hypoxia biomarkers (HIF1, CAIX, GLUT-1) and proliferation marker Ki-67 were analyzed with immunohistochemistry using defined tissue microarrays. Kaplan-Meier methods and Cox proportional hazards regression models were used to investigate prognostic role of the factors. Results: In univariate analyses, strong GLUT-1 positivity and a high Ki-67 index were associated with poor survival. In multivariate model containing clinical prognostic variables, GLUT-1 was an independent prognostic factor associated with worse disease-specific survival (HR 2.9, 95%CI 0.7-12.6,Wald p = 0.15 in the Toronto cohort and HR 3.2, 95%CI 1.3-7.5,Wald p = 0.0085 in the Turku cohort). Conclusion: GLUT-1 is frequently upregulated and is an independent prognostic factor in surgically treated bladder cancer. Further studies are needed to evaluate the potential role of hypoxia-based and targeted therapies in hypoxic bladder tumours.",

keywords = "Bladder cancer, CAIX, GLUT-1, HIF1α, Hypoxia",

author = "Bostr{\"o}m, {P. J.} and J. Thoms and J. Sykes and O. Ahmed and A. Evans and {Van Rhijn}, {B. W.G.} and T. Mirtti and O. Stakhovskyi and M. Laato and D. Margel and M. Pintilie and C. Kuk and M. Milosevic and Zlotta, {A. R.} and Bristow, {R. G.}",

year = "2016",

month = jan,

day = "1",

doi = "10.3233/BLC-150033",

language = "English",

volume = "2",

pages = "101--109",

journal = "Bladder Cancer",

issn = "2352-3727",

publisher = "IOS Press",

number = "1",

}

Boström, PJ, Thoms, J, Sykes, J, Ahmed, O, Evans, A, Van Rhijn, BWG, Mirtti, T, Stakhovskyi, O, Laato, M, Margel, D, Pintilie, M, Kuk, C, Milosevic, M, Zlotta, AR & Bristow, RG 2016, 'Hypoxia marker GLUT-1 (glucose transporter 1) is an independent prognostic factor for survival in bladder cancer patients treated with radical cystectomy', Bladder Cancer, vol. 2, no. 1, pp. 101-109. https://doi.org/10.3233/BLC-150033

TY - JOUR

T1 - Hypoxia marker GLUT-1 (glucose transporter 1) is an independent prognostic factor for survival in bladder cancer patients treated with radical cystectomy

AU - Boström, P. J.

AU - Thoms, J.

AU - Sykes, J.

AU - Ahmed, O.

AU - Evans, A.

AU - Van Rhijn, B. W.G.

AU - Mirtti, T.

AU - Stakhovskyi, O.

AU - Laato, M.

AU - Margel, D.

AU - Pintilie, M.

AU - Kuk, C.

AU - Milosevic, M.

AU - Zlotta, A. R.

AU - Bristow, R. G.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Background: Tumour hypoxia, which is frequent in many cancer types, is associated with treatment resistance and poor prognosis. The role of hypoxia in surgically treated bladder cancer (BC) is not well described. We studied the role of hypoxia in two independent series of urothelial bladder cancers treated with radical cystectomy. Methods: 279 patients from the University Hospital Network (UHN), Toronto, Canada, and Turku University, Finland were studied. Hypoxia biomarkers (HIF1, CAIX, GLUT-1) and proliferation marker Ki-67 were analyzed with immunohistochemistry using defined tissue microarrays. Kaplan-Meier methods and Cox proportional hazards regression models were used to investigate prognostic role of the factors. Results: In univariate analyses, strong GLUT-1 positivity and a high Ki-67 index were associated with poor survival. In multivariate model containing clinical prognostic variables, GLUT-1 was an independent prognostic factor associated with worse disease-specific survival (HR 2.9, 95%CI 0.7-12.6,Wald p = 0.15 in the Toronto cohort and HR 3.2, 95%CI 1.3-7.5,Wald p = 0.0085 in the Turku cohort). Conclusion: GLUT-1 is frequently upregulated and is an independent prognostic factor in surgically treated bladder cancer. Further studies are needed to evaluate the potential role of hypoxia-based and targeted therapies in hypoxic bladder tumours.

AB - Background: Tumour hypoxia, which is frequent in many cancer types, is associated with treatment resistance and poor prognosis. The role of hypoxia in surgically treated bladder cancer (BC) is not well described. We studied the role of hypoxia in two independent series of urothelial bladder cancers treated with radical cystectomy. Methods: 279 patients from the University Hospital Network (UHN), Toronto, Canada, and Turku University, Finland were studied. Hypoxia biomarkers (HIF1, CAIX, GLUT-1) and proliferation marker Ki-67 were analyzed with immunohistochemistry using defined tissue microarrays. Kaplan-Meier methods and Cox proportional hazards regression models were used to investigate prognostic role of the factors. Results: In univariate analyses, strong GLUT-1 positivity and a high Ki-67 index were associated with poor survival. In multivariate model containing clinical prognostic variables, GLUT-1 was an independent prognostic factor associated with worse disease-specific survival (HR 2.9, 95%CI 0.7-12.6,Wald p = 0.15 in the Toronto cohort and HR 3.2, 95%CI 1.3-7.5,Wald p = 0.0085 in the Turku cohort). Conclusion: GLUT-1 is frequently upregulated and is an independent prognostic factor in surgically treated bladder cancer. Further studies are needed to evaluate the potential role of hypoxia-based and targeted therapies in hypoxic bladder tumours.

KW - Bladder cancer

KW - CAIX

KW - GLUT-1

KW - HIF1α

KW - Hypoxia

U2 - 10.3233/BLC-150033

DO - 10.3233/BLC-150033

M3 - Article

AN - SCOPUS:85019172380

SN - 2352-3727

VL - 2

SP - 101

EP - 109

JO - Bladder Cancer

JF - Bladder Cancer

IS - 1

ER -

Hypoxia marker GLUT-1 (glucose transporter 1) is an independent prognostic factor for survival in bladder cancer patients treated with radical cystectomy

Abstract

Keywords

Research Beacons, Institutes and Platforms

UN SDGs

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