Constitutively active AR-V7 plays an essential role in the development and progression of castration-resistant prostate cancer

Yuanyuan Qu, Bo Dai, Dingwei Ye, Yunyi Kong, Kun Chang, Zhongwei Jia, Xiaoqun Yang, Hailiang Zhang, Yao Zhu, Guohai Shi, Yuanyuan Qu, Bo Dai, Dingwei Ye, Yunyi Kong, Kun Chang, Zhongwei Jia, Xiaoqun Yang, Hailiang Zhang, Yao Zhu, Guohai Shi

Abstract

This study aimed to investigate the role of AR-V7 in development of castration-resistant prostate cancer (CRPC) and to determine whether the AR-V7 expression in CRPC tissues can predict cancer-specific survival. We enrolled 100 localized prostate cancer (PCa) (cohort 1), 104 newly diagnosed metastatic PCa (cohort 2), and 46 CRPC (cohort 3) patients treated at our institution. The expression of AR-V7 in PCa was assessed by immunohistochemistry. Cox regression models were used to evaluate the predictive role of all covariates for the development of CRPC in cohort 2 and for cancer-specific survival in cohort 3. Time to CRPC and cancer-specific survival curves were estimated using the Kaplan-Meier method. AR-V7 expression rate in cohort 3 was significantly elevated compared with other two cohorts (p < 0.001). Multivariate analysis revealed that AR-V7 was an independent predictive factor for CRPC development (HR = 2.627, p = 0.001) and for cancer specific survival (HR = 2.247, p = 0.033). Furthermore, the AR-V7 expression was associated with shorter survival in CRPC patients. Our results demonstrated protein AR-V7 levels in primary tumors can be used as a predictive marker for the development of CRPC and as a prognostic factor in CRPC patients. Therapy targeting AR-V7 may help prevent PCa progression and improve the prognosis of CRPC patients.

Figures

Figure 1. The profile of AR-V7 expression…
Figure 1. The profile of AR-V7 expression in cohort 1 (localized PCa), cohort 2 (newly diagnosed metastatic PCa), and cohort 3 (CRPC).
PCa, prostate cancer; CRPC, castration-resistant prostate cancer.
Figure 2. Representative images of immunohistochemical staining…
Figure 2. Representative images of immunohistochemical staining for AR-V7 in (A) cohort 1 (localized PCa), (B) cohort 2 (newly diagnosed metastatic PCa), and (C) cohort 3 (CRPC) tissues (200×).
PCa, prostate cancer; CRPC, castration-resistant prostate cancer.
Figure 3. Kaplan-Meier analysis for time to…
Figure 3. Kaplan-Meier analysis for time to CRPC in cohort 2 according to AR-V7 expression.
CRPC, castration-resistant prostate cancer.
Figure 4. Kaplan-Meier analysis of AR-V7 expression…
Figure 4. Kaplan-Meier analysis of AR-V7 expression in cohort 3 versus cancer-specific survival after TURP.
TURP, transurethral resection of the prostate.

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