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Detection of AR-V7 in Liquid Biopsies of Castrate Resistant Prostate Cancer Patients: A Comparison of AR-V7 Analysis in Circulating Tumor Cells Circulating Tumor RNA and Exosomes

机译:去势抵抗性前列腺癌患者液体活检中AR-V7的检测:循环肿瘤细胞循环肿瘤RNA和外泌体中AR-V7分析的比较

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摘要

Detection of androgen receptor (AR) variant 7 (AR-V7) is emerging as a clinically important biomarker in castrate resistant prostate cancer (CRPC). Detection is possible from tumor tissue, which is often inaccessible in the advanced disease setting. With recent progress in detecting AR-V7 in circulating tumor cells (CTCs), circulating tumor RNA (ctRNA) and exosomes from prostate cancer patients, liquid biopsies have emerged as an alternative to tumor biopsy. Therefore, it is important to clarify whether these approaches differ in sensitivity in order to achieve the best possible biomarker characterization for the patient. In this study, blood samples from 44 prostate cancer patients were processed for CTCs and ctRNA with subsequent AR-V7 testing, while exosomal RNA was isolated from 16 samples and tested. Detection of AR and AR-V7 was performed using a highly sensitive droplet digital PCR-based assay. AR and AR-V7 RNA were detectable in CTCs, ctRNA and exosome samples. AR-V7 detection from CTCs showed higher sensitivity and has proven specificity compared to detection from ctRNA and exosomes. Considering that CTCs are almost always present in the advanced prostate cancer setting, CTC samples should be considered the liquid biopsy of choice for the detection of this clinically important biomarker.
机译:雄激素受体(AR)变体7(AR-V7)的检测正在成为去势抵抗性前列腺癌(CRPC)的临床重要生物标志物。可以从肿瘤组织中进行检测,而在晚期疾病中通常是无法获得的。随着检测循环肿瘤细胞(CTC),循环肿瘤RNA(ctRNA)和前列腺癌患者外来体中AR-V7的最新进展,液体活检已成为肿瘤活检的替代方法。因此,重要的是要弄清楚这些方法的敏感性是否不同,以便为患者获得最佳的生物标志物表征。在这项研究中,对来自44位前列腺癌患者的血液样本进行了CTC和ctRNA的处理,随后进行了AR-V7测试,同时从16个样本中分离了外泌体RNA并进行了测试。 AR和AR-V7的检测使用高度敏感的基于液滴数字PCR的检测方法进行。在CTC,ctRNA和外来体样品中可检测到AR和AR-V7 RNA。与从ctRNA和外泌体中检测相比,从CTC中检测到AR-V7具有更高的灵敏度并证明了其特异性。考虑到在晚期前列腺癌中几乎总是存在CTC,因此应将CTC样品视为检测这种临床上重要的生物标志物的首选液体活检方法。

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