Class III beta-tubulin (TUBB3) expression is recognized as a predictive marker for chemosensitivity to cisplatin- and taxane-based chemotherapies in various malignancies. The aim of this study was to clarify the predictive value of TUBB3 expression for the anticancer effects of first-line cisplatin-based chemotherapy and second-line paclitaxel-based chemotherapy in patients with urothelial cancer (UC).
We reviewed 116 patients with UC (90 with bladder cancer and 27 with upper urinary tract cancer) treated with first-line cisplatin-based chemotherapy. Among them, 42 patients received a paclitaxel-based regimen as second-line chemotherapy for advanced cisplatin-resistant UC. TUBB3 expression was evaluated using immunohistochemistry, and survival analyses were performed using Kaplan-Meier survival curves and multivariate Cox proportional hazard analysis.
TUBB3 was mainly detected in the cytoplasm of cancer cells, and 64 patients (55.2%) were judged as having positive TUBB3 expression. TUBB3 expression was significantly associated with tumour grade (p<0.001). TUBB3 expression was not associated with time to progression after first-line cisplatin-based chemotherapy. However, positive expression of TUBB3 was significantly associated with unfavourable overall survival in patients receiving second-line paclitaxel-based chemotherapy (p=0.021). In addition, a multivariate analysis model including T-stage and metastasis at the beginning of second-line therapy and regimen showed that TUBB3 expression was an independent predictor of poorer survival (hazard ratio(HR)=3.44, 95% confidential interval(CI)=1.15-10.33, p=0.027).
TUBB3 expression was identified as a useful predictive factor for survival after second-line paclitaxel-based therapy in patients with cisplatin-resistant UC. Our results are useful for determining treatment strategies for such patients.
Anticancer research. 2018 Mar [Epub]
Yasuyoshi Miyata, Tomohiro Matsuo, Yuichiro Nakamura, Takuji Yasuda, Kojiro Ohba, Kosuke Takehara, Hideki Sakai
Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan ., Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.