Teo Katy, Gemmell Lisa, Mukherjee Rono, Traynor Pamela, Edwards Joanne
University of Glasgow, Division of Cancer Sciences and Molecular Pathology, Glasgow, Strathclyde, UK.
BJU Int. 2007 Sep;100(3):691-6. doi: 10.1111/j.1464-410X.2007.07001.x. Epub 2007 Jun 2.
To assess the role of selected downstream Bcl-2 family members (Bad, Bax, Bcl-2 and Bcl-xL) in the development of androgen-independent prostate cancer (AIPC), as androgen-deprivation therapy is the treatment of choice in advanced prostate cancer, yet patients generally relapse and progress to an AI state within 18-24 months.
PATIENTS, MATERIALS AND METHODS: The patient cohort was established by retrospectively selecting patients with prostate cancer who had an initial response to androgen-deprivation therapy, but subsequently relapsed with AIPC. In all, 58 patients with prostate cancer were included with matched androgen-dependent (AD) and AI prostate tumours available for immunohistochemical analysis; two independent observers using a weighted-histoscore method scored the staining. Changes in Bad, Bax, Bcl-2 and Bcl-xL expression during transition to AIPC were evaluated and then correlated to known clinical variables.
High Bad expression in AD tumours was associated with an increased time to biochemical relapse (P = 0.007) and a trend towards improved overall survival (P = 0.053). There were also trends towards a decrease in Bad (P = 0.068) and Bax (P = 0.055) expression with progression to AIPC. There were no significant results for Bcl-2 or Bcl-xL.
There is evidence to suggest that Bad expression levels at diagnosis influence time to biochemical relapse and overall survival, and that levels of pro-apoptotic proteins Bad and Bax fall during AIPC development. Bad might therefore represent a possible positive prognostic marker and potential therapeutic target for AIPC in the future.
评估特定下游Bcl-2家族成员（Bad、Bax、Bcl-2和Bcl-xL）在雄激素非依赖性前列腺癌（AIPC）发生发展中的作用，因为雄激素剥夺疗法是晚期前列腺癌的首选治疗方法，但患者通常会在18 - 24个月内复发并进展为雄激素非依赖状态。
患者、材料与方法：通过回顾性选择对雄激素剥夺疗法有初始反应但随后复发为AIPC的前列腺癌患者建立患者队列。总共纳入58例前列腺癌患者，有配对的雄激素依赖性（AD）和雄激素非依赖前列腺肿瘤可用于免疫组织化学分析；两名独立观察者使用加权组织学评分法对染色进行评分。评估向AIPC转变过程中Bad、Bax、Bcl-2和Bcl-xL表达的变化，然后将其与已知临床变量相关联。
AD肿瘤中高Bad表达与生化复发时间延长相关（P = 0.007），且有总体生存改善的趋势（P = 0.053）。随着进展为AIPC，Bad（P = 0.068）和Bax（P = 0.055）表达也有下降趋势。Bcl-2或Bcl-xL无显著结果。
有证据表明诊断时的Bad表达水平影响生化复发时间和总体生存，且在AIPC发生发展过程中促凋亡蛋白Bad和Bax的水平下降。因此，Bad可能代表未来AIPC的一种可能的阳性预后标志物和潜在治疗靶点。
