一种源自全血中前列腺癌增强转录本的双基因检测对转移性去势抵抗性前列腺癌的生存具有预后价值并可预测治疗获益。

A 2-Gene Panel Derived From Prostate Cancer-Enhanced Transcripts in Whole Blood Is Prognostic for Survival and Predicts Treatment Benefit in Metastatic Castration-Resistant Prostate Cancer.

作者信息

Heck Matthias M, Thalgott Mark, Schmid Sebastian C, Oh William K, Gong Yixuan, Wang Li, Zhu Jun, Seitz Anna-Katharina, Porst Desiree, Höppner Michael, Retz Margitta, Gschwend Jürgen E, Nawroth Roman

机构信息

Department of Urology, Klinikum rechts der Isar, Technical University of Munich, München, Germany.

Department of Hematology/Oncology, Mount Sinai Hospital, The Tisch Cancer Institute, New York, New York.

出版信息

Prostate. 2016 Sep;76(13):1160-8. doi: 10.1002/pros.23202. Epub 2016 May 16.

DOI:10.1002/pros.23202

PMID:27198487

Abstract

BACKGROUND

To determine a prognostic model derived from prostate cancer-enhanced transcripts in whole blood of castration-resistant prostate cancer (CRPC) patients and explore its applicability as a surrogate of treatment response.

METHODS

Six out of twenty-three selected transcripts were identified as specific for detection of metastatic prostate cancer cells in peripheral blood using quantitative polymerase chain reaction (qPCR). Their prognostic value was explored in whole blood samples of a training cohort (n = 22 CRPC patients, New York, USA). A resulting 2-gene panel (2GP) including KLK2 and TMPRSS2 was validated in an independent cohort with pre- and post-treatment blood draws after 9-16 weeks of systemic treament (n = 86 CRPC patients, Munich, Germany). Overall survival (OS), prostate-specific antigen progression-free survival (PSA-PFS), and clinical PFS were analyzed. Kaplan-Meier and cox regression analyses were performed.

RESULTS

An unfavorable 2GP (≥1 marker positive) identified patients with poor survival (median OS 10.0 months [95%CI 5.7-14.2] vs. not reached; P = 0.023). This was validated in an independent cohort at pre-treatment (median OS 7.8 [95%CI 6.5-9.2] vs. 17.3 months [95%CI 10.7-23.8]; P = 0.004) and post-treatment blood draw (median OS 5.0 [95%CI 0.0-10.0] vs. 18.0 months [95%CI 9.5-26.6]; P = 0.003). The 2GP independently predicted OS on multivariate analysis (hazard ratio 2.1 [95%CI 1.1-4.0]; P = 0.034) and performed better than PSA decline at correlation with OS. Conversion to favorable 2GP during treatment correlated with improved OS (7.8 to 20.9 months), PSA-PFS (2.8 to 12.0 months), and clinical PFS (4.6 to 8.0 months).

CONCLUSIONS

The established 2GP is prognostic for survival at pre- and post-treatment blood draw in CRPC patients and conversion to favorable 2GP predicts treatment benefit. Prostate 76:1160-1168, 2016. © 2016 Wiley Periodicals, Inc.

摘要

背景

确定一种基于去势抵抗性前列腺癌（CRPC）患者全血中前列腺癌增强转录本的预后模型，并探讨其作为治疗反应替代指标的适用性。

方法

使用定量聚合酶链反应（qPCR）从23个选定的转录本中鉴定出6个对检测外周血中转移性前列腺癌细胞具有特异性的转录本。在一个训练队列（n = 22例CRPC患者，美国纽约）的全血样本中探讨它们的预后价值。一个由KLK2和TMPRSS2组成的双基因组合（2GP）在一个独立队列中进行验证，该队列在全身治疗9 - 16周后进行治疗前和治疗后采血（n = 86例CRPC患者，德国慕尼黑）。分析总生存期（OS）、前列腺特异性抗原无进展生存期（PSA - PFS）和临床无进展生存期。进行了Kaplan - Meier分析和cox回归分析。

结果

不良的2GP（≥1个标志物阳性）识别出生存期较差的患者（中位OS 10.0个月[95%CI 5.7 - 14.2] vs. 未达到；P = 0.023）。这在一个独立队列的治疗前（中位OS 7.8[95%CI 6.5 - 9.2] vs. 17.3个月[95%CI 10.7 - 23.8]；P = 0.004）和治疗后采血时（中位OS 5.0[95%CI 0.0 - 10.0] vs. 18.0个月[95%CI 9.5 - 26.6]；P = 0.003）得到验证。2GP在多变量分析中独立预测OS（风险比2.1[95%CI 1.1 - 4.0]；P = 0.034），并且在与OS的相关性方面比PSA下降表现更好。治疗期间转化为良好的2GP与OS改善（7.8至20.9个月）、PSA - PFS改善（2.8至12.0个月）和临床PFS改善（4.6至8.0个月）相关。