Department of Pathology, Tulane University School of Medicine, New Orleans, Louisiana; Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana.
Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana; Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana; Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana.
J Urol. 2016 Dec;196(6):1758-1763. doi: 10.1016/j.juro.2016.06.095. Epub 2016 Jul 20.
Most prostate cancer mortality can be attributed to metastatic castration resistant prostate cancer, an advanced stage that remains incurable despite recent advances. The AR (androgen receptor) signaling axis remains active in castration resistant prostate cancer. Recent studies suggest that expression of the AR-V (AR splice variant) AR-V7 may underlie resistance to abiraterone and enzalutamide. However, controversy exists over the optimal assay. Our objective was to develop a fast and sensitive assay for AR-Vs in patients.
Two approaches were assessed in this study. The first approach was based on depletion of leukocytes and the second one used RNA purified directly from whole blood preserved in PAXgene® tubes. Transcript expression was analyzed by quantitative reverse transcription-polymerase chain reaction.
Through a side-by-side comparison we found that the whole blood approach was suitable to detect AR-Vs. The specificity of the assay was corroborated in a cancer-free cohort. Using the PAXgene assay samples from a cohort of 46 patients with castration resistant prostate cancer were analyzed. Overall, AR-V7 and AR were detected in 67.53% and 29.87% of samples, respectively. Statistical analysis revealed a strong association of AR-V positivity with a history of second line hormonal therapies.
To our knowledge this is the first study to demonstrate that PAXgene preserved whole blood can be used to obtain clinically relevant information regarding the expression of 2 AR-Vs. These data on a castration resistant prostate cancer cohort support a role for AR-Vs in resistance to therapies targeting the AR ligand-binding domain.
大多数前列腺癌死亡可归因于转移性去势抵抗性前列腺癌，尽管最近取得了进展，但这种晚期疾病仍然无法治愈。雄激素受体（AR）信号通路在去势抵抗性前列腺癌中仍然活跃。最近的研究表明，AR 剪接变异体（AR-V）AR-V7 的表达可能是导致阿比特龙和恩杂鲁胺耐药的原因。然而，对于最佳检测方法仍存在争议。我们的目的是为患者开发一种快速灵敏的 AR-V 检测方法。
本研究评估了两种方法。第一种方法基于白细胞耗竭，第二种方法使用直接从保存在 PAXgene®管中的全血中纯化的 RNA。通过定量逆转录聚合酶链反应分析转录表达。
通过平行比较，我们发现全血方法适合检测 AR-Vs。该检测方法的特异性在无癌队列中得到了证实。使用 PAXgene 检测方法，对 46 例去势抵抗性前列腺癌患者的样本进行了分析。总体而言，AR-V7 和 AR 分别在 67.53%和 29.87%的样本中检测到。统计分析显示，AR-V 阳性与二线激素治疗史密切相关。
据我们所知，这是第一项证明 PAXgene 保存的全血可用于获得与 AR-V 表达相关的临床相关信息的研究。这些针对去势抵抗性前列腺癌患者的研究数据支持 AR-V 在抵抗靶向 AR 配体结合域的治疗中的作用。
