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基于尿液外泌体检测转移性去势抵抗性前列腺癌患者雄激素受体变异体7

Urinary exosome-based androgen receptor-variant 7 detection in metastatic castration-resistant prostate cancer patients.

作者信息

Wang Chao, Liu Xiang, Li Hongyan, Zhao Libo, Kong Guanyi, Chen Jing, Li Zhi, Qi Jianfei, Tian Ye, Zhang Fengbo

机构信息

Department of Urology, Beijing Pinggu Hospital, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

Echo Biotech Co., Ltd, Beijing, China.

出版信息

Transl Androl Urol. 2022 Feb;11(2):202-212. doi: 10.21037/tau-21-1136.

Abstract

BACKGROUND

Androgen receptor variant 7 (AR-V7) detection provides important information for the clinical management of abiraterone in metastatic castration-resistant prostate cancer (mCRPC). We performed a non-invasive urine-derived exosomal AR-V7 analysis of mCRPC patients.

METHODS

A total of 34 mCRPC patients were recruited including 16 patients treated with abiraterone (ABI) with stable prostate-specific antigen (PSA)/radiograph response (the ABI-Sta group) and 18 were resistant to abiraterone (the ABI-Res group). Urine was collected from patients and healthy control patients for the analysis. Exosomal ribonucleic acid was isolated from urine. Urinary exosome-based androgen receptor-variant 7 was detected by quantitative real-time polymerase chain reaction assay. Characteristics of patients and survival data were collected. The correlation between AR-V7 expression and the therapeutic effect/survival outcomes of abiraterone was analyzed.

RESULTS

Urine is the ideal biological sample for exosome separation and AR full-length analysis. Positive urine-derived exosomal AR-V7 was detected in 32.4% (11 of 34) of the mCRPC patients' urine samples. Positive AR-V7 was more common in the ABI-Res patients than the ABI-Sta patients (50.0% 12.5%, respectively; P=0.009), and was associated with a higher PSA progression rate and poorer overall survival (OS) (P=0.0031, and P=0.0012, respectively).

CONCLUSIONS

The present study showed that the detection of urine-derived exosomal AR-V7 provides a sensitive and feasible clinical workflow. The predicting role of urine-derived exosomal AR-V7 in mCRPC patients should be further verified using studies with greater sample sizes.

摘要

背景

雄激素受体变异体7(AR-V7)检测为转移性去势抵抗性前列腺癌(mCRPC)中阿比特龙的临床管理提供重要信息。我们对mCRPC患者进行了非侵入性尿液来源外泌体AR-V7分析。

方法

共招募34例mCRPC患者,其中16例接受阿比特龙(ABI)治疗且前列腺特异性抗原(PSA)/影像学反应稳定(ABI-Sta组),18例对阿比特龙耐药(ABI-Res组)。收集患者及健康对照者的尿液进行分析。从尿液中分离外泌体核糖核酸。采用定量实时聚合酶链反应检测尿液外泌体中的雄激素受体变异体7。收集患者特征及生存数据。分析AR-V7表达与阿比特龙治疗效果/生存结局之间的相关性。

结果

尿液是外泌体分离和AR全长分析的理想生物样本。在34例mCRPC患者的尿液样本中,32.4%(11/34)检测到尿液来源外泌体AR-V7阳性。AR-V7阳性在ABI-Res组患者中比ABI-Sta组患者更常见(分别为50.0%和12.5%;P = 0.009),且与更高的PSA进展率和更差的总生存期(OS)相关(分别为P = 0.0031和P = 0.0012)。

结论

本研究表明,尿液来源外泌体AR-V7检测提供了一种敏感且可行的临床工作流程。尿液来源外泌体AR-V7在mCRPC患者中的预测作用应通过更大样本量的研究进一步验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8736/8899142/68ac41b93ad3/tau-11-02-202-f1.jpg

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