循环肿瘤细胞（CTC）、全长雄激素受体（AR-FL）和雄激素受体剪接变体7（AR-V7）在去势抵抗性转移性前列腺癌患者前瞻性队列中的作用
Role of Circulating Tumor Cells (CTC), Androgen Receptor Full Length (AR-FL) and Androgen Receptor Splice Variant 7 (AR-V7) in a Prospective Cohort of Castration-Resistant Metastatic Prostate Cancer Patients.
作者信息
Cattrini Carlo, Rubagotti Alessandra, Zinoli Linda, Cerbone Luigi, Zanardi Elisa, Capaia Matteo, Barboro Paola, Boccardo Francesco
机构信息
Academic Unit of Medical Oncology, IRCCS San Martino Polyclinic Hospital, 16132 Genoa, Italy.
Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genoa, 16132 Genoa, Italy.
出版信息
Cancers (Basel). 2019 Sep 13;11(9):1365. doi: 10.3390/cancers11091365.
BACKGROUND
Circulating tumor cells (CTC), androgen receptor full-length (AR-FL), and androgen receptor splice variant 7 (AR-V7) are prognostic in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). AR-V7 seems to predict resistance to androgen-receptor signaling inhibitors (ARSi).
METHODS
We assessed the association of CTC, AR-FL, and AR-V7 with prostate-specific antigen (PSA) response and overall survival (OS). We used a modified AdnaTest CTC-based AR-FL and AR-V7 mRNA assay. Chi-square test, Fisher Exact test, Kaplan-Meier method, log-rank test, Cox proportional hazards models were used as appropriate.
RESULTS
We enrolled 39 mCRPC pts, of those 24 started a first-line treatment for mCRPC (1L subgroup) and 15 had received at least two lines for mCRPC (>2L subgroup). CTC, AR-FL, and AR-V7 were enriched in >2L compared to 1L subgroup. Detection of these biomarkers was associated with a lower percentage of biochemical responses. Only 1/7 AR-V7+ pts had a PSA response and received cabazitaxel. Median OS was 4.7 months (95% CI 0.6-8.9) in AR-V7+ pts and not reached in AR-V7- pts. AR-V7 was the only variable with prognostic significance in the Cox model.
CONCLUSION
AR-V7, CTC, and AR-FL are associated with advanced mCRPC and AR-V7+ predicts for shorter OS.
背景
循环肿瘤细胞（CTC）、雄激素受体全长（AR-FL）和雄激素受体剪接变体7（AR-V7）对转移性去势抵抗性前列腺癌（mCRPC）患者具有预后价值。AR-V7似乎可预测对雄激素受体信号抑制剂（ARSi）的耐药性。
方法
我们评估了CTC、AR-FL和AR-V7与前列腺特异性抗原（PSA）反应及总生存期（OS）之间的关联。我们使用了一种基于改良AdnaTest CTC的AR-FL和AR-V7 mRNA检测方法。根据情况使用卡方检验、Fisher精确检验、Kaplan-Meier法、对数秩检验、Cox比例风险模型。
结果
我们纳入了39例mCRPC患者，其中24例开始了mCRPC的一线治疗（1L亚组），15例接受了至少两线mCRPC治疗（>2L亚组）。与1L亚组相比，>2L亚组中CTC、AR-FL和AR-V7更为富集。这些生物标志物的检测与较低的生化反应百分比相关。仅1/7的AR-V7阳性患者有PSA反应并接受了卡巴他赛治疗。AR-V7阳性患者的中位OS为4.7个月（95%CI 0.6-8.9），AR-V7阴性患者未达到。在Cox模型中，AR-V7是唯一具有预后意义的变量。
结论
AR-V7、CTC和AR-FL与晚期mCRPC相关，AR-V7阳性预测较短的OS。
Zotero 插件