Role of serum response factor expression in prostate cancer biochemical recurrence

Background: Up to a third of prostate cancer patients fail curative treatment strategiessuch as surgery and radiation therapy in the form of biochemical recurrence (BCR) whichcan be predictive of poor outcome. Recent clinical trials have shown that menexperiencing BCR might benefit from earlier intervention post-radical prostatectomy(RP). Therefore, there is an urgent need to identify earlier prognostic biomarkers whichwill guide clinicians in making accurate diagnosis and timely decisions on the nextappropriate treatment. The objective of this study was to evaluate Serum ResponseFactor (SRF) protein expression following RP and to investigate its association with BCR.Materials and Methods: SRF nuclear expression was evaluated by immunohistochemistry(IHC) in TMAs across three international radical prostatectomy cohorts for a totalof 615 patients. Log-rank test and Kaplan-Meier analyses were used for BCRcomparisons. Stepwise backwards elimination proportional hazard regression analysiswas used to explore the significance of SRF in predicting BCR in the context of otherclinical pathological variables. Area under the curve (AUC) values were generated bysimulating repeated random sub-samples.Results: Analysis of the immunohistochemical staining of benign versus cancer coresshowed higher expression of nuclear SRF protein expression in cancer cores comparedwith benign for all the three TMAs analysed (P < 0.001, n = 615). Kaplan-Meier curves ofthe three TMAs combined showed that patients with higher SRF nuclear expression hada shorter time to BCR compared with patients with lower SRF expression (P < 0.001,n = 215). Together with pathological T stage T3, SRF was identified as a predictor of BCRusing stepwise backwards elimination proportional hazard regression analysis(P = 0.0521). Moreover ROC curves and AUC values showed that SRF was betterthan T stage in predicting BCR at year 3 and 5 following radical prostatectomy, thecombination of SRF and T stage had a higher AUC value than the two taken separately.Conclusions: SRF assessment by IHC following RP could be useful in guiding cliniciansto better identify patients for appropriate follow-up and timely treatment.