Validation of survivin and HMGA2 as biomarkers for cisplatin resistance in bladder cancer

Ulrich Krafft, Stephan Tschirdewahn, Jochen Hess, Nina N. Harke, Boris Hadaschik, Csilla Olah, Susanne Krege, P. Nyírády, Attila Szendröi, Miklós Szücs, Orsolya Módos, Eszter Székely, Henning Reis, Tibor Szarvas

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Objectives: Cisplatin-based chemotherapy represents the gold standard in the treatment of advanced bladder cancer (BC) both in the neoadjuvant and adjuvant setting. Since novel immunooncologic agents are available for cisplatin-resistant or ineligible patients, biological markers for the prediction of cisplatin resistance become more important in treatment decisions. Therefore, we aimed to assess the therapy predictive value of 8 promising tissue biomarkers with regard to cisplatin therapy. Methods: Emmprin, survivin, HMGA2, MTA1, RhoGDI, PEG10, TGM2, and TLN1 expressions were analyzed in paraffin-embedded bladder cancer tissue samples of 106 patients who underwent adjuvant or salvage cisplatin-based chemotherapy by using immunohistochemistry. Results were correlated with the clinicopathological and follow-up data by performing both univariable and multivariable survival analyses. Results: Higher HMGA2 nuclear staining intensity and positive survivin nuclear staining were associated with worse overall survival (OS) (P = 0.045 and P = 0.002, respectively). In accordance, survivin nuclear staining also significantly correlated with shorter progression free survival (PFS, P = 0.024), while HMGA2 nuclear positivity tended to correlate with shorter PFS (P = 0.069) after at least 2 cycles of chemotherapy. In the multivariable analyses only survivin remained as an independent predictor of both OS and PFS (P = 0.008 and P = 0.025). None of the other markers proved to be significant predictors of adjuvant or salvage cisplatin-based chemotherapy. Conclusions: Our results demonstrate that survivin represents a promising marker for the prediction of cisplatin resistance in BC. In addition the therapy predictive role of HMGA2 should be further investigated. Immunohistochemical analysis of BC samples provides a feasible way for the prediction of cisplatin-resistance and may therefore provide a valuable tool for optimizing treatment decisions in advanced BC.

Original languageEnglish
JournalUrologic Oncology: Seminars and Original Investigations
DOIs
Publication statusPublished - Jan 1 2019

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Urinary Bladder Neoplasms
Cisplatin
Biomarkers
Drug Therapy
Staining and Labeling
CD147 Antigens
Therapeutics
Survival
Survival Analysis
Paraffin
Disease-Free Survival
Immunohistochemistry

Keywords

  • Bladder cancer
  • Cisplatin
  • EMMPRIN
  • HMGA2
  • Resistance
  • Survivin

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Validation of survivin and HMGA2 as biomarkers for cisplatin resistance in bladder cancer. / Krafft, Ulrich; Tschirdewahn, Stephan; Hess, Jochen; Harke, Nina N.; Hadaschik, Boris; Olah, Csilla; Krege, Susanne; Nyírády, P.; Szendröi, Attila; Szücs, Miklós; Módos, Orsolya; Székely, Eszter; Reis, Henning; Szarvas, Tibor.

In: Urologic Oncology: Seminars and Original Investigations, 01.01.2019.

Research output: Contribution to journalArticle

Krafft, U, Tschirdewahn, S, Hess, J, Harke, NN, Hadaschik, B, Olah, C, Krege, S, Nyírády, P, Szendröi, A, Szücs, M, Módos, O, Székely, E, Reis, H & Szarvas, T 2019, 'Validation of survivin and HMGA2 as biomarkers for cisplatin resistance in bladder cancer', Urologic Oncology: Seminars and Original Investigations. https://doi.org/10.1016/j.urolonc.2019.04.015
Krafft, Ulrich ; Tschirdewahn, Stephan ; Hess, Jochen ; Harke, Nina N. ; Hadaschik, Boris ; Olah, Csilla ; Krege, Susanne ; Nyírády, P. ; Szendröi, Attila ; Szücs, Miklós ; Módos, Orsolya ; Székely, Eszter ; Reis, Henning ; Szarvas, Tibor. / Validation of survivin and HMGA2 as biomarkers for cisplatin resistance in bladder cancer. In: Urologic Oncology: Seminars and Original Investigations. 2019.
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abstract = "Objectives: Cisplatin-based chemotherapy represents the gold standard in the treatment of advanced bladder cancer (BC) both in the neoadjuvant and adjuvant setting. Since novel immunooncologic agents are available for cisplatin-resistant or ineligible patients, biological markers for the prediction of cisplatin resistance become more important in treatment decisions. Therefore, we aimed to assess the therapy predictive value of 8 promising tissue biomarkers with regard to cisplatin therapy. Methods: Emmprin, survivin, HMGA2, MTA1, RhoGDI, PEG10, TGM2, and TLN1 expressions were analyzed in paraffin-embedded bladder cancer tissue samples of 106 patients who underwent adjuvant or salvage cisplatin-based chemotherapy by using immunohistochemistry. Results were correlated with the clinicopathological and follow-up data by performing both univariable and multivariable survival analyses. Results: Higher HMGA2 nuclear staining intensity and positive survivin nuclear staining were associated with worse overall survival (OS) (P = 0.045 and P = 0.002, respectively). In accordance, survivin nuclear staining also significantly correlated with shorter progression free survival (PFS, P = 0.024), while HMGA2 nuclear positivity tended to correlate with shorter PFS (P = 0.069) after at least 2 cycles of chemotherapy. In the multivariable analyses only survivin remained as an independent predictor of both OS and PFS (P = 0.008 and P = 0.025). None of the other markers proved to be significant predictors of adjuvant or salvage cisplatin-based chemotherapy. Conclusions: Our results demonstrate that survivin represents a promising marker for the prediction of cisplatin resistance in BC. In addition the therapy predictive role of HMGA2 should be further investigated. Immunohistochemical analysis of BC samples provides a feasible way for the prediction of cisplatin-resistance and may therefore provide a valuable tool for optimizing treatment decisions in advanced BC.",
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AU - Krafft, Ulrich

AU - Tschirdewahn, Stephan

AU - Hess, Jochen

AU - Harke, Nina N.

AU - Hadaschik, Boris

AU - Olah, Csilla

AU - Krege, Susanne

AU - Nyírády, P.

AU - Szendröi, Attila

AU - Szücs, Miklós

AU - Módos, Orsolya

AU - Székely, Eszter

AU - Reis, Henning

AU - Szarvas, Tibor

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N2 - Objectives: Cisplatin-based chemotherapy represents the gold standard in the treatment of advanced bladder cancer (BC) both in the neoadjuvant and adjuvant setting. Since novel immunooncologic agents are available for cisplatin-resistant or ineligible patients, biological markers for the prediction of cisplatin resistance become more important in treatment decisions. Therefore, we aimed to assess the therapy predictive value of 8 promising tissue biomarkers with regard to cisplatin therapy. Methods: Emmprin, survivin, HMGA2, MTA1, RhoGDI, PEG10, TGM2, and TLN1 expressions were analyzed in paraffin-embedded bladder cancer tissue samples of 106 patients who underwent adjuvant or salvage cisplatin-based chemotherapy by using immunohistochemistry. Results were correlated with the clinicopathological and follow-up data by performing both univariable and multivariable survival analyses. Results: Higher HMGA2 nuclear staining intensity and positive survivin nuclear staining were associated with worse overall survival (OS) (P = 0.045 and P = 0.002, respectively). In accordance, survivin nuclear staining also significantly correlated with shorter progression free survival (PFS, P = 0.024), while HMGA2 nuclear positivity tended to correlate with shorter PFS (P = 0.069) after at least 2 cycles of chemotherapy. In the multivariable analyses only survivin remained as an independent predictor of both OS and PFS (P = 0.008 and P = 0.025). None of the other markers proved to be significant predictors of adjuvant or salvage cisplatin-based chemotherapy. Conclusions: Our results demonstrate that survivin represents a promising marker for the prediction of cisplatin resistance in BC. In addition the therapy predictive role of HMGA2 should be further investigated. Immunohistochemical analysis of BC samples provides a feasible way for the prediction of cisplatin-resistance and may therefore provide a valuable tool for optimizing treatment decisions in advanced BC.

AB - Objectives: Cisplatin-based chemotherapy represents the gold standard in the treatment of advanced bladder cancer (BC) both in the neoadjuvant and adjuvant setting. Since novel immunooncologic agents are available for cisplatin-resistant or ineligible patients, biological markers for the prediction of cisplatin resistance become more important in treatment decisions. Therefore, we aimed to assess the therapy predictive value of 8 promising tissue biomarkers with regard to cisplatin therapy. Methods: Emmprin, survivin, HMGA2, MTA1, RhoGDI, PEG10, TGM2, and TLN1 expressions were analyzed in paraffin-embedded bladder cancer tissue samples of 106 patients who underwent adjuvant or salvage cisplatin-based chemotherapy by using immunohistochemistry. Results were correlated with the clinicopathological and follow-up data by performing both univariable and multivariable survival analyses. Results: Higher HMGA2 nuclear staining intensity and positive survivin nuclear staining were associated with worse overall survival (OS) (P = 0.045 and P = 0.002, respectively). In accordance, survivin nuclear staining also significantly correlated with shorter progression free survival (PFS, P = 0.024), while HMGA2 nuclear positivity tended to correlate with shorter PFS (P = 0.069) after at least 2 cycles of chemotherapy. In the multivariable analyses only survivin remained as an independent predictor of both OS and PFS (P = 0.008 and P = 0.025). None of the other markers proved to be significant predictors of adjuvant or salvage cisplatin-based chemotherapy. Conclusions: Our results demonstrate that survivin represents a promising marker for the prediction of cisplatin resistance in BC. In addition the therapy predictive role of HMGA2 should be further investigated. Immunohistochemical analysis of BC samples provides a feasible way for the prediction of cisplatin-resistance and may therefore provide a valuable tool for optimizing treatment decisions in advanced BC.

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KW - Cisplatin

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KW - HMGA2

KW - Resistance

KW - Survivin

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