PO.CL01.23 · 临床研究
CTC 计数和 AR-V7 表达与转移性前列腺癌对雄激素受体抑制剂耐药性临床相关性的初步研究
Pilot study of the clinical correlation of CTC counts and AR-V7 expression with resistance to androgen receptor inhibitors in metastatic prostate cancer
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摘要 Abstract
中文摘要
引言
雄激素受体剪接变体 7（AR-V7）是雄激素受体的一种组成型活性异构体，已被证实与对 AR 靶向疗法的耐药及进展为转移性前列腺癌（mPCa）相关。然而，基于组织的 AR-V7 检测受限于转移灶的可及性差，尤其是在治疗前后。为解决这一局限，我们使用 CytoGen 的 Smart Biopsy™ CTC 平台开发了一种基于 CTC 的 AR-V7 检测系统，并研究了 CTC 计数和 AR-V7 表达与雄激素受体抑制剂（ARI）的临床关联。
方法
使用 Smart Biopsy™ 细胞分离器处理来自 12 例 mPCa 患者的外周血样本（20 mL），以进行 CTC 富集。使用来自健康供者的 5 例样本作为免疫荧光法 CTC 计数的阴性对照及 AR-V7 表达的临界值。通过免疫荧光（IF）对 CTC 进行计数，并使用微滴式数字 PCR（ddPCR）分析 AR-V7 转录本。
结果
为研究 CTC 计数和 AR-V7 表达与 ARI 耐药性的临床相关性，采集了 mPCa 患者的血液样本，并使用 Smart Biopsy™ 细胞分离器进行 CTC 富集。全部 12 例 mPCa 患者样本中的 CTC 数量均通过 IF 检测成功计数。10 例患者显示高 CTC 负荷（每 5mL 血液 ≥10 个 CTC），且其与 ARI 耐药性存在统计学显著相关。还通过 ddPCR 检测了 CTC 中的 AR-V7 表达。12 例 mPCa 患者中有 5 例显示 AR-V7 阳性 CTC，且 5 例中有 4 例与 ARI 耐药性相关。
结论
在这项初步研究中，CTC 计数和/或 CTC 中的 AR-V7 检测与 ARI 耐药性显示出有意义的相关性，提示它们可能作为预测 ARI 治疗反应的潜在诊断工具。
查看英文原文 English abstract
Introduction
Androgen receptor splice variant 7 (AR-V7) is a constitutively active isoform of the androgen receptor and has been associated with resistance to AR-targeting therapies and progression to metastatic prostate cancer (mPCa). However, tissue-based detection of AR-V7 is limited by the poor accessibility of metastatic lesions, particularly before and after treatment. To address this limitation, we developed a CTC-based AR-V7 detection system using CytoGen's Smart Biopsy™ CTC platform and investigated the clinical association of CTC counts and AR-V7 expression androgen receptor inhibitor (ARI).
Method
Peripheral blood samples (20 mL) from 12 mPCa patients were processed using the Smart Biopsy™ Cell Isolator for CTC enrichment. 5 samples from healthy donor were used as negative control of CTC counts by immunofluorescence and the cut-off of AR-V7 expression. CTCs were enumerated by immunofluorescence (IF), and AR-V7 transcripts were analyzed using droplet digital PCR (ddPCR)
Results
To investigate the clinical correlation of CTC counts and AR-V7 expression to the resistance of ARI, blood samples of mPCa patients were collected and CTC enrichment was proceeded with Smart Biopsy™ Cell Isolator. Number of CTC in all of 12 mPCa patients' samples were successfully counted by IF assay. 10 patients showed the high CTC burden (≥10 CTCs per 5mL of blood) and it was statistically significant correlation with the resistance of ARI. AR-V7 expression in CTC were also tested by ddPCR. 5 out of 12 mPCa patients showed AR-V7 positive CTC and 4 out of 5 patients were associated with ARI's resistance.
Conclusions
In this pilot study, CTC counts and/or AR-V7 detection in CTC showed the meaningful correlation to the resistance of ARI, suggesting that they may serve as potential diagnostic tools for predicting the treatment response of ARI.
利益披露 Disclosure
J. Lee,
CytoGen Employment.
M. Hwang,
CytoGen Employment.
S. Kim,
CytoGen Employment.
C. Kim, None.
J. Kim,
CytoGen Employment.