循环肿瘤细胞 HOXB13 RNA 检测对接受阿比特龙或恩杂鲁胺治疗的转移性去势抵抗性前列腺癌（mCRPC）男性的影响。

The Impact of Circulating Tumor Cell HOXB13 RNA Detection in Men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated with Abiraterone or Enzalutamide.

机构信息

Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina.

Department of Medicine, Duke Prostate and Urologic Cancer Center, Duke Cancer Institute, Duke University, Durham, North Carolina.

出版信息

Clin Cancer Res. 2024 Mar 15;30(6):1152-1159. doi: 10.1158/1078-0432.CCR-23-3017.

DOI:10.1158/1078-0432.CCR-23-3017

PMID:38236581

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10947837/

Abstract

PURPOSE

HOXB13 is an androgen receptor (AR) coregulator specifically expressed in cells of prostatic lineage. We sought to associate circulating tumor cell (CTC) HOXB13 expression with outcomes in men with mCRPC treated with abiraterone or enzalutamide.

EXPERIMENTAL DESIGN

We conducted a retrospective analysis of the multicenter prospective PROPHECY trial of mCRPC men (NCT02269982, n = 118) treated with abiraterone/enzalutamide. CTC detection and HOXB13 complementary DNA (cDNA) expression was measured using a modified Adnatest, grouping patients into 3 categories: CTC 0 (undetectable); CTC+ HOXB13 CTC low (<4 copies); or CTC+ HOXB13 CTC high. The HOXB13 threshold was determined by maximally selected rank statistics for prognostic associations with overall survival (OS) and progression-free survival (PFS).

RESULTS

We included 102 men with sufficient CTC HOXB13 cDNA, identifying 25%, 31%, and 44% of patients who were CTC 0, CTC+ HOXB13 low, and CTC+ HOXB13 high, respectively. Median OS were 25.7, 27.8, and 12.1 months whereas the median PFS were 9.0, 7.7, and 3.8 months, respectively. In subgroup analysis among men with CellSearch CTCs ≥5 copies/mL and adjusting for prior abi/enza treatment and Halabi clinical risk score, the multivariate HR for HOXB13 CTC detection was 2.39 (95% CI, 1.06-5.40) for OS and 2.78 (95% CI, 1.38-5.59) for PFS, respectively. Low HOXB13 CTC detection was associated with lower CTC PSA, PSMA, AR-FL, and AR-V7 detection, and more liver/lung metastases (41% vs. 25%).

CONCLUSIONS

Higher CTC HOXB13 expression is associated with AR-dependent biomarkers in CTCs and is adversely prognostic in the context of potent AR inhibition in men with mCRPC.

摘要

目的

HOXB13 是一种雄激素受体 (AR) 共调节剂，特异性表达于前列腺细胞系。我们试图将循环肿瘤细胞 (CTC) HOXB13 的表达与接受阿比特龙或恩杂鲁胺治疗的 mCRPC 男性的结局联系起来。

实验设计

我们对多中心前瞻性 PROPHECY 试验中接受阿比特龙/恩杂鲁胺治疗的 mCRPC 男性（NCT02269982，n=118）进行了回顾性分析。使用改良的 Adnatest 检测 CTC 并测量 HOXB13 互补 DNA (cDNA) 表达，将患者分为 3 组：CTC0（不可检测）；CTC+ HOXB13 CTC 低（<4 拷贝）；或 CTC+ HOXB13 CTC 高。HOXB13 阈值通过与总生存 (OS) 和无进展生存 (PFS) 相关的最大选择秩统计确定。

结果

我们纳入了 102 名具有足够 CTC HOXB13 cDNA 的男性，分别确定了 25%、31%和 44%的患者为 CTC0、CTC+ HOXB13 低和 CTC+ HOXB13 高。中位 OS 分别为 25.7、27.8 和 12.1 个月，而中位 PFS 分别为 9.0、7.7 和 3.8 个月。在 CellSearch CTCs≥5 个/毫升的男性亚组分析中，并调整了先前的 abi/enza 治疗和 Halabi 临床风险评分，HOXB13 CTC 检测的多变量 HR 分别为 OS 的 2.39（95%CI，1.06-5.40）和 PFS 的 2.78（95%CI，1.38-5.59）。低 HOXB13 CTC 检测与 CTCs 中较低的 PSA、PSMA、AR-FL 和 AR-V7 检测以及更多的肝/肺转移（41%比 25%）相关。