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

Urol Oncol. 2019 Nov;37(11):810.e7-810.e15. doi: 10.1016/j.urolonc.2019.04.015. Epub 2019 Apr 30.

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.

Keywords: Bladder cancer; Cisplatin; EMMPRIN; HMGA2; Resistance; Survivin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / metabolism
  • Cisplatin / therapeutic use*
  • Drug Resistance, Neoplasm*
  • Female
  • HMGA2 Protein / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Progression-Free Survival
  • Survival Rate
  • Survivin / metabolism*
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • BIRC5 protein, human
  • Biomarkers, Tumor
  • HMGA2 Protein
  • HMGA2 protein, human
  • Survivin
  • Cisplatin