High insulin-like growth factor mRNA-binding protein 3 (IMP3) protein expression is associated with poor survival in muscle-invasive bladder cancer

Tibor Szarvas, Frank Vom Dorp, Christian Niedworok, Ariane Melchior-Becker, Jens W. Fischer, Bernhard B. Singer, Henning Reis, Ágnes Bánkfalvi, Kurt W. Schmid, I. Romics, Süleyman Ergün, Herbert Rübben

Research output: Contribution to journalArticle

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Abstract

Objective To assess the prognostic value and molecular actions of the oncofetal protein insulin-like growth factor mRNA-binding protein 3 (IMP3) in muscle-invasive bladder cancer (BC). Patients and Methods IMP3 expression was analysed by immunohistochemistry, real-time polymerase chain reaction and Western blot analysis in 224 patients with BC. The molecular targets of IMP3; CD44, insulin-like growth factor 2 (IGF2) and its receptor the IGF1 receptor (IGF1-R) were also investigated. Expression levels were correlated with clinical follow-up data by using both univariate and multivariate Cox regression analyses. Results IMP3 mRNA and protein levels were significantly elevated in high-stage and high-grade muscle-invasive BC. In muscle-invasive BC IMP3 protein but not gene expression proved to be an independent predictor of disease-specific (hazard ratio [HR] 2.58, 95% confidence interval [CI] 1.28-4.56, P = 0.004) and overall survival (HR 2.07, 95% CI 1.12-3.82, P = 0.020). The expression levels of IGF2 and CD44 showed no correlation with that of IMP3. Conclusions High IMP3 protein levels may identify patients with BC at high risk of disease progression and may therefore select patients for a more intensive therapy or for a strict follow-up. Its high expression in high-grade bladder carcinoma cells makes IMP3 for an attractive target for therapy. The tumour promoting effect of IMP3 is independent from its regulatory action on IGF2 and CD44 expression.

Original languageEnglish
JournalBJU International
Volume110
Issue number6B
DOIs
Publication statusPublished - Sep 2012

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Insulin-Like Growth Factor Binding Protein 3
Urinary Bladder Neoplasms
Muscles
Messenger RNA
Survival
Proteins
Somatomedins
Confidence Intervals
Disease Progression
Real-Time Polymerase Chain Reaction
Urinary Bladder
Western Blotting
Immunohistochemistry
Regression Analysis
Carcinoma
Gene Expression

Keywords

  • bladder cancer
  • CD44
  • IGF2
  • IGF2BP3
  • IMP3
  • KOC1
  • prognosis

ASJC Scopus subject areas

  • Urology

Cite this

High insulin-like growth factor mRNA-binding protein 3 (IMP3) protein expression is associated with poor survival in muscle-invasive bladder cancer. / Szarvas, Tibor; Dorp, Frank Vom; Niedworok, Christian; Melchior-Becker, Ariane; Fischer, Jens W.; Singer, Bernhard B.; Reis, Henning; Bánkfalvi, Ágnes; Schmid, Kurt W.; Romics, I.; Ergün, Süleyman; Rübben, Herbert.

In: BJU International, Vol. 110, No. 6B, 09.2012.

Research output: Contribution to journalArticle

Szarvas, T, Dorp, FV, Niedworok, C, Melchior-Becker, A, Fischer, JW, Singer, BB, Reis, H, Bánkfalvi, Á, Schmid, KW, Romics, I, Ergün, S & Rübben, H 2012, 'High insulin-like growth factor mRNA-binding protein 3 (IMP3) protein expression is associated with poor survival in muscle-invasive bladder cancer', BJU International, vol. 110, no. 6B. https://doi.org/10.1111/j.1464-410X.2012.11149.x
Szarvas, Tibor ; Dorp, Frank Vom ; Niedworok, Christian ; Melchior-Becker, Ariane ; Fischer, Jens W. ; Singer, Bernhard B. ; Reis, Henning ; Bánkfalvi, Ágnes ; Schmid, Kurt W. ; Romics, I. ; Ergün, Süleyman ; Rübben, Herbert. / High insulin-like growth factor mRNA-binding protein 3 (IMP3) protein expression is associated with poor survival in muscle-invasive bladder cancer. In: BJU International. 2012 ; Vol. 110, No. 6B.
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abstract = "Objective To assess the prognostic value and molecular actions of the oncofetal protein insulin-like growth factor mRNA-binding protein 3 (IMP3) in muscle-invasive bladder cancer (BC). Patients and Methods IMP3 expression was analysed by immunohistochemistry, real-time polymerase chain reaction and Western blot analysis in 224 patients with BC. The molecular targets of IMP3; CD44, insulin-like growth factor 2 (IGF2) and its receptor the IGF1 receptor (IGF1-R) were also investigated. Expression levels were correlated with clinical follow-up data by using both univariate and multivariate Cox regression analyses. Results IMP3 mRNA and protein levels were significantly elevated in high-stage and high-grade muscle-invasive BC. In muscle-invasive BC IMP3 protein but not gene expression proved to be an independent predictor of disease-specific (hazard ratio [HR] 2.58, 95{\%} confidence interval [CI] 1.28-4.56, P = 0.004) and overall survival (HR 2.07, 95{\%} CI 1.12-3.82, P = 0.020). The expression levels of IGF2 and CD44 showed no correlation with that of IMP3. Conclusions High IMP3 protein levels may identify patients with BC at high risk of disease progression and may therefore select patients for a more intensive therapy or for a strict follow-up. Its high expression in high-grade bladder carcinoma cells makes IMP3 for an attractive target for therapy. The tumour promoting effect of IMP3 is independent from its regulatory action on IGF2 and CD44 expression.",
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AU - Szarvas, Tibor

AU - Dorp, Frank Vom

AU - Niedworok, Christian

AU - Melchior-Becker, Ariane

AU - Fischer, Jens W.

AU - Singer, Bernhard B.

AU - Reis, Henning

AU - Bánkfalvi, Ágnes

AU - Schmid, Kurt W.

AU - Romics, I.

AU - Ergün, Süleyman

AU - Rübben, Herbert

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N2 - Objective To assess the prognostic value and molecular actions of the oncofetal protein insulin-like growth factor mRNA-binding protein 3 (IMP3) in muscle-invasive bladder cancer (BC). Patients and Methods IMP3 expression was analysed by immunohistochemistry, real-time polymerase chain reaction and Western blot analysis in 224 patients with BC. The molecular targets of IMP3; CD44, insulin-like growth factor 2 (IGF2) and its receptor the IGF1 receptor (IGF1-R) were also investigated. Expression levels were correlated with clinical follow-up data by using both univariate and multivariate Cox regression analyses. Results IMP3 mRNA and protein levels were significantly elevated in high-stage and high-grade muscle-invasive BC. In muscle-invasive BC IMP3 protein but not gene expression proved to be an independent predictor of disease-specific (hazard ratio [HR] 2.58, 95% confidence interval [CI] 1.28-4.56, P = 0.004) and overall survival (HR 2.07, 95% CI 1.12-3.82, P = 0.020). The expression levels of IGF2 and CD44 showed no correlation with that of IMP3. Conclusions High IMP3 protein levels may identify patients with BC at high risk of disease progression and may therefore select patients for a more intensive therapy or for a strict follow-up. Its high expression in high-grade bladder carcinoma cells makes IMP3 for an attractive target for therapy. The tumour promoting effect of IMP3 is independent from its regulatory action on IGF2 and CD44 expression.

AB - Objective To assess the prognostic value and molecular actions of the oncofetal protein insulin-like growth factor mRNA-binding protein 3 (IMP3) in muscle-invasive bladder cancer (BC). Patients and Methods IMP3 expression was analysed by immunohistochemistry, real-time polymerase chain reaction and Western blot analysis in 224 patients with BC. The molecular targets of IMP3; CD44, insulin-like growth factor 2 (IGF2) and its receptor the IGF1 receptor (IGF1-R) were also investigated. Expression levels were correlated with clinical follow-up data by using both univariate and multivariate Cox regression analyses. Results IMP3 mRNA and protein levels were significantly elevated in high-stage and high-grade muscle-invasive BC. In muscle-invasive BC IMP3 protein but not gene expression proved to be an independent predictor of disease-specific (hazard ratio [HR] 2.58, 95% confidence interval [CI] 1.28-4.56, P = 0.004) and overall survival (HR 2.07, 95% CI 1.12-3.82, P = 0.020). The expression levels of IGF2 and CD44 showed no correlation with that of IMP3. Conclusions High IMP3 protein levels may identify patients with BC at high risk of disease progression and may therefore select patients for a more intensive therapy or for a strict follow-up. Its high expression in high-grade bladder carcinoma cells makes IMP3 for an attractive target for therapy. The tumour promoting effect of IMP3 is independent from its regulatory action on IGF2 and CD44 expression.

KW - bladder cancer

KW - CD44

KW - IGF2

KW - IGF2BP3

KW - IMP3

KW - KOC1

KW - prognosis

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