Class III β-Tubulin Expression Predicts Prostate Tumor Aggressiveness and Patient Response to Docetaxel-Based Chemotherapy

Expression of class III beta-tubulin (beta III-tubulin) correlates with tumor progression and resistance to taxane-based therapies for several human malignancies, but its use as a biomarker of tumor behavior in prostate cancer (PCa) remains largely unexplored. Here, we describe beta III-tubulin immunohistochemical staining patterns of prostate tumors obtained from a broad spectrum of PCa patients, some of whom subsequently received docetaxel therapy for castration-resistant PCa (CRPC). Elevated beta III-tubulin expression was significantly associated with tumor aggressiveness in PCa patients with presumed localized disease, as it was found to be an independent marker of biochemical recurrence after treatment. Additionally, beta III-tubulin expression in tumor cells was an independent predictor of lower overall survival for patients receiving docetaxel-based chemotherapy for CRPC. Manipulation of beta III-tubulin expression in human PCa cell lines using a human beta III-tubulin expression vector or beta III-tubulin small interfering RNA altered cell survival in response to docetaxel treatment in a manner that supports a role for beta III-tubulin expression as a mediator of PCa cell resistance to docetaxel therapy. Our findings suggest a role for beta III-tubulin as candidate theranostic biomarker to predict the response to docetaxel-based chemotherapy as well as to target for treatment of docetaxel-resistant CRPC. Cancer Res; 70(22); 9253-64. (C) 2010 AACR.