Validation of Survivin and HMGA2 As Biomarkers for Cisplatin Resistance in Bladder Cancer

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.