通过血液液体活检检测前列腺癌循环肿瘤细胞中 PSMA 的表达。

Q3 Medicine
Journal of Circulating Biomarkers Pub Date : 2024-02-21 eCollection Date: 2024-01-01 DOI:10.33393/jcb.2024.2636
Santosh Gupta, Luisa Fernandez, David Bourdon, Anis A Hamid, Anupama Pasam, Ernest Lam, Richard Wenstrup, Shahneen Sandhu
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引用次数: 0

摘要

背景:对于mCRPC患者,PSMA靶向放射性配体治疗已显著改善了临床疗效。一种基于血液的液体活检检测方法可识别循环肿瘤细胞上的 PSMA 蛋白表达,这有助于更好地为治疗决策提供信息,并确定最有可能从 PSMA 靶向放射性配体治疗中获益的患者:方法:利用高通量成像和数字人工智能病理学算法,开发了一种四色免疫荧光检测法,用于发现玻璃载玻片上CTC上的PSMA蛋白表达。使用添加到健康供血中的细胞系细胞(LNCaP/PC3s/22Rv1)来研究该检测方法的精确度、特异性、灵敏度、检测限和总体准确性。利用 3 毫升血液对 PSMA-PET 阳性的高风险 mCRPC 患者(24 人)进行了临床验证和低通滤波全基因组测序:PSMA CTC IF 分析法的特异性、灵敏度和总体准确度均高于 99%,且精确度高。在临床验证中,76%(16/21)的病例为 PSMA 阳性,伴有 CTC 异质性,88%(21/24)的患者每毫升血液中至少含有一个常规 CTC。来自11名mCRPC患者的36个低通量序列CTC经常表现出AR和MYC的拷贝数增加,以及RB1、PTEN、TP53和BRCA2位点的丢失:利用Epic Sciences的液体活检CTC平台进行的分析验证表明,它有潜力检测mCRPC患者CTC中PSMA蛋白的表达。在许多正在进行的针对表达 PSMA 的肿瘤的临床研究中,该检测方法被定位为评估 PSMA 表达、异质性和治疗反应的有效研究工具。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Detection of PSMA expression on circulating tumor cells by blood-based liquid biopsy in prostate cancer.

Background: For patients with mCRPC, PSMA-targeted radioligand treatment has significantly improved the clinical outcome. A blood-based liquid biopsy assay for recognizing PSMA protein expression on circulating tumor cells may be beneficial for better informing therapeutic decision-making and identifying the patients most likely to benefit from PSMA-targeted radioligand therapy.

Methods: Using high-throughput imaging and digital AI pathology algorithms, a four-color immunofluorescence assay has been developed to find PSMA protein expression on CTCs on a glass slide. Cell line cells (LNCaP/PC3s/22Rv1) spiked into healthy donor blood were used to study the precision, specificity, sensitivity, limit of detection, and overall accuracy of the assay. Clinical validation and low-pass whole-genome sequencing were performed in PSMA-PET-positive patients with high-risk mCRPC (N = 24) utilizing 3 mL of blood.

Results: The PSMA CTC IF assay achieved analytical specificity, sensitivity, and overall accuracy above 99% with high precision. In the clinical validation, 76% (16/21) of the cases were PSMA positive with CTC heterogeneity, and 88% (21/24) of the patients contained at least one conventional CTC per milliliter of blood. Thirty-six low-pass-sequenced CTCs from 11 individuals with mCRPC frequently exhibited copy number increases in AR and MYC and losses in RB1, PTEN, TP53, and BRCA2 locus.

Conclusions: The analytical validation utilizing Epic Sciences' liquid biopsy CTC platform demonstrated the potential to detect PSMA protein expression in CTCs from patients with mCRPC. This assay is positioned as an effective research tool to evaluate PSMA expression, heterogeneity, and therapeutic response in many ongoing clinical studies to target tumors that express PSMA.

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来源期刊
Journal of Circulating Biomarkers
Journal of Circulating Biomarkers Medicine-Biochemistry (medical)
CiteScore
3.20
自引率
0.00%
发文量
9
审稿时长
8 weeks
期刊介绍: Journal of Circulating Biomarkers is an international, peer-reviewed, open access scientific journal focusing on all aspects of the rapidly growing field of circulating blood-based biomarkers and diagnostics using circulating protein and lipid markers, circulating tumor cells (CTC), circulating cell-free DNA (cfDNA) and extracellular vesicles, including exosomes, microvesicles, microparticles, ectosomes and apoptotic bodies. The journal publishes high-impact articles that deal with all fields related to circulating biomarkers and diagnostics, ranging from basic science to translational and clinical applications. Papers from a wide variety of disciplines are welcome; interdisciplinary studies are especially suitable for this journal. Included within the scope are a broad array of specialties including (but not limited to) cancer, immunology, neurology, metabolic diseases, cardiovascular medicine, regenerative medicine, nosology, physiology, pathology, technological applications in diagnostics, therapeutics, vaccine, drug delivery, regenerative medicine, drug development and clinical trials. The journal also hosts reviews, perspectives and news on specific topics.
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