Association of AR-V7 and Prostate-Specific Antigen RNA Levels in Blood with Efficacy of Abiraterone Acetate and Enzalutamide Treatment in Men with Prostate Cancer.
Association of AR-V7 and Prostate-Specific Antigen RNA Levels in Blood with Efficacy of Abiraterone Acetate and Enzalutamide Treatment in Men with Prostate Cancer.
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DOI：
10.1158/1078-0432.ccr-16-1070
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发表时间：
2017-02-01
期刊：
影响因子：
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通讯作者：
Kantoff PW
中科院分区：
文献类型：
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作者：
Qu F;Xie W;Nakabayashi M;Zhang H;Jeong SH;Wang X;Komura K;Sweeney CJ;Sartor O;Lee GM;Kantoff PW
我们评价了抗去势前列腺癌(CRPC)患者外周血中前列腺特异性抗原(PSA)和雄激素受体剪接变异体-7(AR-V7)转录水平与治疗失败时间(TTF)和总生存期(OS)的关系。在接受AA(N=81)或苯扎鲁胺(N=51)治疗CRPC的回顾性队列中，治疗前采集的外周血中AR-V7和PSA的RNA水平用Droplet Digital-PCR进行定量。经已知预后因素调整后的多变量Cox回归用于分析。在接受AA治疗的患者中有57%的患者检测到PSA转录本，在接受苯扎鲁胺治疗的患者中检测到63%的PSA转录本。PSA阳性患者的TTF值明显短于PSA阴性患者(调整后HR分别为2.2 7(95%CI：1.2 6，4.10)和2.6 0(95%CI：1.19，5.69)；AA组和苯扎鲁胺组的p值分别为0.006和0.017)。在单因素分析中，AR-V7转录本水平较高的患者使用AA和苯扎鲁胺的总有效时间较短(AA组的中位数为8.0月，P=0.046；苯扎鲁胺组的中位数为3.6月，P=0.050)。在多变量模型中，在苯扎鲁胺-队列中与总转移因子的相关性仍然显著(调整后的HR=2.02；95%CI：1.01，4.05；p=0.048)，但在AA-队列中无统计学意义。在这两个队列中，我们观察到PSA和AR-V7RNA在OS上的潜在预后价值；可检测到PSA转录本和AR-V7高的患者预测OS最差。血液中的PSA和AR-V7转录本可能成为预测AA或苯扎鲁胺治疗TTF和OS的生物标志物。如果前瞻性验证，它们的检测可能会更容易，而不需要分离循环中的肿瘤细胞。
We evaluated the association of prostate specific antigen (PSA) and androgen receptor splice variant-7 (AR-V7) transcript levels in patients’ blood with time to treatment failure (TTF) and overall survival (OS) with abiraterone acetate (AA) and/or enzalutamide treatment in castration resistant prostate cancer (CRPC) patients. RNA levels of AR-V7 and PSA in peripheral blood collected before treatment were quantified using Droplet Digital-PCR in retrospective cohorts treated with AA (N=81) or enzalutamide (N=51) for CRPC. Multivariable Cox regression adjusted for known prognostic factors was used for analyses. PSA-transcripts were detected in 57% of AA-treated patients and in 63% of enzalutamide-treated patients. PSA-positive patients had a shorter TTF than PSA-negative patients (adjusted-HR=2.27 (95%CI: 1.26, 4.10) and 2.60 (95%CI: 1.19, 5.69); p-value=0.006 and 0.017 in AA and enzalutamide cohorts, respectively). Patients with a higher-AR-V7 transcript level had a shorter TTF with AA and enzalutamide in univariate analysis (median 8.0 versus 15.6 months, p=0.046 in AA-cohort and 3.6 versus 5.6 months, p=0.050 in enzalutamide-cohort). In multivariable models, the association with TTF remained significant in the enzalutamide-cohort (adjusted-HR=2.02; 95%CI:1.01, 4.05; p=0.048), but statistically insignificant in the AA-cohort. In both cohorts, we observed potential prognostic value of both PSA and AR-V7 RNA expression on OS; patients with detectable PSA transcripts and high AR-V7 predicted the poorest OS. PSA and AR-V7 transcripts in blood potentially serve as biomarkers predicting TTF and OS with AA or enzalutamide treatment. If validated prospectively, their detection could be facilitated without isolation of circulating tumor cells.