Loss of expression of the tumour suppressor gene AIMP3 predicts survival following radiotherapy in muscle-invasive bladder cancerCitation formats

  • External authors:
  • Pratik M S Gurung
  • Abhi Veerakumarasivam
  • Magali Williamson
  • Nicholas Counsell
  • James Douglas
  • Wei S. Tan
  • Andrew Feber
  • Simon J. Crabb
  • Susan C. Short
  • Alex Freeman
  • Thomas Powles
  • John D. Kelly

Standard

Loss of expression of the tumour suppressor gene AIMP3 predicts survival following radiotherapy in muscle-invasive bladder cancer. / Gurung, Pratik M S; Veerakumarasivam, Abhi; Williamson, Magali; Counsell, Nicholas; Douglas, James; Tan, Wei S.; Feber, Andrew; Crabb, Simon J.; Short, Susan C.; Freeman, Alex; Powles, Thomas; Hoskin, Peter; West, Catharine M.; Kelly, John D.

In: International Journal of Cancer, 2014.

Research output: Contribution to journalArticle

Harvard

Gurung, PMS, Veerakumarasivam, A, Williamson, M, Counsell, N, Douglas, J, Tan, WS, Feber, A, Crabb, SJ, Short, SC, Freeman, A, Powles, T, Hoskin, P, West, CM & Kelly, JD 2014, 'Loss of expression of the tumour suppressor gene AIMP3 predicts survival following radiotherapy in muscle-invasive bladder cancer', International Journal of Cancer. https://doi.org/10.1002/ijc.29022

APA

Gurung, P. M. S., Veerakumarasivam, A., Williamson, M., Counsell, N., Douglas, J., Tan, W. S., ... Kelly, J. D. (2014). Loss of expression of the tumour suppressor gene AIMP3 predicts survival following radiotherapy in muscle-invasive bladder cancer. International Journal of Cancer. https://doi.org/10.1002/ijc.29022

Vancouver

Gurung PMS, Veerakumarasivam A, Williamson M, Counsell N, Douglas J, Tan WS et al. Loss of expression of the tumour suppressor gene AIMP3 predicts survival following radiotherapy in muscle-invasive bladder cancer. International Journal of Cancer. 2014. https://doi.org/10.1002/ijc.29022

Author

Gurung, Pratik M S ; Veerakumarasivam, Abhi ; Williamson, Magali ; Counsell, Nicholas ; Douglas, James ; Tan, Wei S. ; Feber, Andrew ; Crabb, Simon J. ; Short, Susan C. ; Freeman, Alex ; Powles, Thomas ; Hoskin, Peter ; West, Catharine M. ; Kelly, John D. / Loss of expression of the tumour suppressor gene AIMP3 predicts survival following radiotherapy in muscle-invasive bladder cancer. In: International Journal of Cancer. 2014.

Bibtex

@article{8f17478f2f5c456a8878ddd5e06efed4,
title = "Loss of expression of the tumour suppressor gene AIMP3 predicts survival following radiotherapy in muscle-invasive bladder cancer",
abstract = "The aim of this study was to test the utility of AIMP3, an upstream regulator of DNA damage response following genotoxic stress, as a clinical biomarker in muscle-invasive bladder cancer (MIBC). AIMP3 was identified from a meta-analysis of a global gene-expression dataset. AIMP3 protein expression was determined by immunohistochemistry on a customised bladder cancer tissue-microarray (TMA). The mechanism of gene silencing was probed using methylation-specific PCR. The association between AIMP3 expression, Tp53 transactivity and genomic stability was analysed. In vitro AIMP3 translocation to the nucleus in response to ionising radiation was demonstrated using immunofluorescence. Radiosensitisation effects of siRNA-mediated AIMP3-knockdown were measured using colony forming assays. TMAs derived from patients enrolled in BCON, a Phase III multicentre radiotherapy trial in bladder cancer (ISRCTN45938399) were used to evaluate the association between AIMP3 expression and survival. The prognostic value of AIMP3 expression was determined in a TMA derived from patients treated by radical cystectomy. Loss of AIMP3 expression was frequent in MIBC and associated with impaired Tp53 transactivity and genomic instability. AIMP3-knockdown was associated with an increase in radioresistance. Loss of AIMP3 expression was associated with survival in MIBC patients following radiotherapy (HR=0.53; 95{\%} CI: 0.36 to 0.78, p = 0.002) but was not prognostic in the cystectomy set. In conclusion, AIMP3 expression is lost in a subset of bladder cancers and is significantly predictive of survival following radiotherapy in MIBC patients. {\circledC} 2014 UICC.",
keywords = "AIMP3, Biomarker, Bladder cancer, Organ-preservation, Radiotherapy",
author = "Gurung, {Pratik M S} and Abhi Veerakumarasivam and Magali Williamson and Nicholas Counsell and James Douglas and Tan, {Wei S.} and Andrew Feber and Crabb, {Simon J.} and Short, {Susan C.} and Alex Freeman and Thomas Powles and Peter Hoskin and West, {Catharine M.} and Kelly, {John D.}",
note = "10065, Cancer Research UK, United Kingdom",
year = "2014",
doi = "10.1002/ijc.29022",
language = "English",
journal = "International journal of cancer. Journal international du cancer",
issn = "0020-7136",
publisher = "John Wiley & Sons Ltd",

}

RIS

TY - JOUR

T1 - Loss of expression of the tumour suppressor gene AIMP3 predicts survival following radiotherapy in muscle-invasive bladder cancer

AU - Gurung, Pratik M S

AU - Veerakumarasivam, Abhi

AU - Williamson, Magali

AU - Counsell, Nicholas

AU - Douglas, James

AU - Tan, Wei S.

AU - Feber, Andrew

AU - Crabb, Simon J.

AU - Short, Susan C.

AU - Freeman, Alex

AU - Powles, Thomas

AU - Hoskin, Peter

AU - West, Catharine M.

AU - Kelly, John D.

N1 - 10065, Cancer Research UK, United Kingdom

PY - 2014

Y1 - 2014

N2 - The aim of this study was to test the utility of AIMP3, an upstream regulator of DNA damage response following genotoxic stress, as a clinical biomarker in muscle-invasive bladder cancer (MIBC). AIMP3 was identified from a meta-analysis of a global gene-expression dataset. AIMP3 protein expression was determined by immunohistochemistry on a customised bladder cancer tissue-microarray (TMA). The mechanism of gene silencing was probed using methylation-specific PCR. The association between AIMP3 expression, Tp53 transactivity and genomic stability was analysed. In vitro AIMP3 translocation to the nucleus in response to ionising radiation was demonstrated using immunofluorescence. Radiosensitisation effects of siRNA-mediated AIMP3-knockdown were measured using colony forming assays. TMAs derived from patients enrolled in BCON, a Phase III multicentre radiotherapy trial in bladder cancer (ISRCTN45938399) were used to evaluate the association between AIMP3 expression and survival. The prognostic value of AIMP3 expression was determined in a TMA derived from patients treated by radical cystectomy. Loss of AIMP3 expression was frequent in MIBC and associated with impaired Tp53 transactivity and genomic instability. AIMP3-knockdown was associated with an increase in radioresistance. Loss of AIMP3 expression was associated with survival in MIBC patients following radiotherapy (HR=0.53; 95% CI: 0.36 to 0.78, p = 0.002) but was not prognostic in the cystectomy set. In conclusion, AIMP3 expression is lost in a subset of bladder cancers and is significantly predictive of survival following radiotherapy in MIBC patients. © 2014 UICC.

AB - The aim of this study was to test the utility of AIMP3, an upstream regulator of DNA damage response following genotoxic stress, as a clinical biomarker in muscle-invasive bladder cancer (MIBC). AIMP3 was identified from a meta-analysis of a global gene-expression dataset. AIMP3 protein expression was determined by immunohistochemistry on a customised bladder cancer tissue-microarray (TMA). The mechanism of gene silencing was probed using methylation-specific PCR. The association between AIMP3 expression, Tp53 transactivity and genomic stability was analysed. In vitro AIMP3 translocation to the nucleus in response to ionising radiation was demonstrated using immunofluorescence. Radiosensitisation effects of siRNA-mediated AIMP3-knockdown were measured using colony forming assays. TMAs derived from patients enrolled in BCON, a Phase III multicentre radiotherapy trial in bladder cancer (ISRCTN45938399) were used to evaluate the association between AIMP3 expression and survival. The prognostic value of AIMP3 expression was determined in a TMA derived from patients treated by radical cystectomy. Loss of AIMP3 expression was frequent in MIBC and associated with impaired Tp53 transactivity and genomic instability. AIMP3-knockdown was associated with an increase in radioresistance. Loss of AIMP3 expression was associated with survival in MIBC patients following radiotherapy (HR=0.53; 95% CI: 0.36 to 0.78, p = 0.002) but was not prognostic in the cystectomy set. In conclusion, AIMP3 expression is lost in a subset of bladder cancers and is significantly predictive of survival following radiotherapy in MIBC patients. © 2014 UICC.

KW - AIMP3

KW - Biomarker

KW - Bladder cancer

KW - Organ-preservation

KW - Radiotherapy

U2 - 10.1002/ijc.29022

DO - 10.1002/ijc.29022

M3 - Article

JO - International journal of cancer. Journal international du cancer

JF - International journal of cancer. Journal international du cancer

SN - 0020-7136

ER -