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表达前列腺特异性膜抗原(PSMA)的循环肿瘤细胞表明原发性非转移性三阴性乳腺癌的预后较差。

Circulating Tumor Cells Expressing the Prostate Specific Membrane Antigen (PSMA) Indicate Worse Outcome in Primary, Non-Metastatic Triple-Negative Breast Cancer.

作者信息

Kasimir-Bauer Sabine, Keup Corinna, Hoffmann Oliver, Hauch Siegfried, Kimmig Rainer, Bittner Ann-Kathrin

机构信息

Department of Gynecology and Obstetrics, University Hospital of Essen, Essen, Germany.

QIAGEN GmbH, Hilden, Germany.

出版信息

Front Oncol. 2020 Sep 3;10:1658. doi: 10.3389/fonc.2020.01658. eCollection 2020.

Abstract

We analyzed mRNA profiles of prostate cancer related genes in circulating tumor cells (CTCs) of primary, non-metastatic triple-negative breast cancer (TNBC) patients (pts) before and after neoadjuvant chemotherapy to elucidate the potential of prostate cancer targets in this BC subgroup. Blood from 41 TNBC pts ( = 41 before / 26 after therapy) was analyzed for CTCs applying the AdnaTest EMT-2/Stem Cell Select. Multimarker RT-qPCR allowed the detection of the prostate specific antigen , the prostate specific membrane antigen , full-length androgen receptor (), and AR splice-variant seven (). Before therapy, at least one prostate cancer related gene was detected in 15/41 pts (37%). Notably, in 73% of positive cases, was co-expressed. After therapy, CTCs of only one patient harbored prostate cancer related genes. + and + CTCs significantly correlated with early relapse ( = 0.041; = 0.00039) whereas + CTCs also associated with a reduced OS ( = 0.0059). This correlation was confirmed for + CTCs in univariate (PFS = 0.002; OS = 0.015), but not multivariate analysis. Although CTCs that expressed prostate cancer related genes were eliminated by the given therapy, + CTCs significantly identified pts at high risk for relapse. Furthermore, AR inhibition, often discussed for this BC subgroup, might not be successful in the primary setting of the disease since we identified + CTCs together with + CTCs, associated with therapeutic failure.

摘要

我们分析了原发性非转移性三阴性乳腺癌(TNBC)患者新辅助化疗前后循环肿瘤细胞(CTC)中前列腺癌相关基因的mRNA谱,以阐明该乳腺癌亚组中前列腺癌靶点的潜力。应用AdnaTest EMT-2/干细胞选择法对41例TNBC患者(治疗前41例/治疗后26例)的血液进行CTC分析。多标记逆转录定量聚合酶链反应(Multimarker RT-qPCR)可检测前列腺特异性抗原、前列腺特异性膜抗原、全长雄激素受体(AR)和AR剪接变体7(AR-V7)。治疗前,41例患者中有15例(37%)检测到至少一种前列腺癌相关基因。值得注意的是,在73%的阳性病例中,AR-V7与AR共同表达。治疗后,仅1例患者的CTC含有前列腺癌相关基因。AR+和AR-V7+CTC与早期复发显著相关(P = 0.041;P = 0.00039),而AR+CTC也与总生存期(OS)缩短相关(P = 0.0059)。单因素分析中,AR+CTC的这种相关性得到证实(无进展生存期[PFS]P = 0.002;OS P = 0.015),但多因素分析未得到证实。尽管表达前列腺癌相关基因的CTC被既定治疗消除,但AR+CTC显著识别出复发高危患者。此外,该乳腺癌亚组常讨论的AR抑制在疾病的初始阶段可能不成功,因为我们发现AR+CTC与AR-V7+CTC一起与治疗失败相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91e9/7497312/557aeb26fc38/fonc-10-01658-g0001.jpg

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