波形蛋白和Ki67在去势抵抗性前列腺癌来源的循环肿瘤细胞中的表达
Vimentin and Ki67 expression in circulating tumour cells derived from castrate-resistant prostate cancer.
作者信息
Lindsay C R, Le Moulec S, Billiot F, Loriot Y, Ngo-Camus M, Vielh P, Fizazi K, Massard C, Farace F
机构信息
INSERM U981, University of Paris-Sud XI, Translational Research Laboratory, Gustave Roussy Cancer Campus, Villejuif, France.
Department of Medical Oncology, Bergonie Cancer Institute, Bordeaux, France.
出版信息
BMC Cancer. 2016 Feb 29;16:168. doi: 10.1186/s12885-016-2192-6.
BACKGROUND
High circulating tumor cell (CTC) counts are associated with poor prognosis in advanced prostate cancer, and recently CTC number was suggested to be a surrogate for survival in metastatic castrate-resistant prostate cancer (mCRPC). Ki67 and vimentin are well-characterised markers of tumour cell proliferation and the epithelial-mesenchymal transition (EMT), respectively. Here we asked if the expression of vimentin and Ki67 in CTCs offered prognostic or predictive information in mCRPC.
METHODS
In two separate patient cohorts, anti-vimentin or anti-Ki67 antibodies were added to the free channel in the CellSearch® system for analysis of peripheral blood samples. For each cohort, association of CTC number with clinical characteristics were assessed using Fisher's exact, Mann-Whitney and chi-squared tests. Kaplan-Meier method and log-rank tests were used to analyse overall survival (OS) of vimentin-expressing and Ki67-expressing CTC patient cohorts.
RESULTS
In this retrospective analysis, CTC vimentin expression was analysed in 142 blood samples from 93 patients, and CTC Ki67 expression was analysed in 90 blood samples from 51 patients. In the vimentin cohort, 80/93 (86 %) of baseline samples from patients were CTC-positive overall (≥1 total CTC per 7.5 mls blood), and 30/93 (32.3 %) vimentin CTC-positive (≥1 vimentin-positive CTC per 7.5 mls blood). 41/51 (80.4 %) of baseline samples from patients in the Ki67 cohort were CTC-positive overall, and 23/51 (45.1 %) Ki67 CTC-positive (≥1 Ki67-positive CTC per 7.5 mls blood). There was no significant difference in baseline PSA in patients with vimentin-positive CTC at baseline versus those with no vimentin-positive CTC at baseline (p = 0.33). A significant reduction in OS was shown in patients with vimentin-positive CTC compared to those without vimentin-positive CTC (median 305 days vs 453 days, p = 0.0293). There was no significant difference in baseline PSA in patients with Ki67-positive CTC at baseline versus those without Ki67-positive CTC (p = 0.228), but OS was significantly reduced in the Ki67-positive CTC group (median 512 days vs 751 days, p = 0.0091). No changes in relative proportion of vimentin- or Ki67-positive CTCs were observed in post-treatment samples compared to baseline.
CONCLUSIONS
Analysis of vimentin and Ki67 expression can straightforwardly be assessed in CTCs from patients with mCRPC. Poorer survival outcomes were observed in vimentin- and Ki67-positive CTC patients.
TRANSLATIONAL STUDY PROTOCOLS
CEC-CTC (IDRCB2008-AOO585-50) and Petrus ( NCT01786031 ).
背景
循环肿瘤细胞（CTC）计数高与晚期前列腺癌的不良预后相关，最近有研究表明，CTC数量可作为转移性去势抵抗性前列腺癌（mCRPC）生存情况的替代指标。Ki67和波形蛋白分别是肿瘤细胞增殖和上皮-间质转化（EMT）的典型标志物。在此，我们探讨了CTC中波形蛋白和Ki67的表达是否能为mCRPC提供预后或预测信息。
方法
在两个独立的患者队列中，将抗波形蛋白或抗Ki67抗体添加到CellSearch®系统的游离通道中，用于分析外周血样本。对于每个队列，使用Fisher精确检验、Mann-Whitney检验和卡方检验评估CTC数量与临床特征的相关性。采用Kaplan-Meier法和对数秩检验分析波形蛋白表达阳性和Ki67表达阳性的CTC患者队列的总生存期（OS）。
结果
在这项回顾性分析中，对93例患者的142份血样进行了CTC波形蛋白表达分析，并对51例患者的90份血样进行了CTC Ki67表达分析。在波形蛋白队列中，患者基线样本中80/93（86%）总体CTC呈阳性（每7.5毫升血液中≥1个总CTC），30/93（32.3%）波形蛋白CTC呈阳性（每7.5毫升血液中≥1个波形蛋白阳性CTC）。Ki67队列中患者基线样本的41/51（80.4%）总体CTC呈阳性，23/51（45.1%）Ki67 CTC呈阳性（每7.5毫升血液中≥1个Ki-67阳性CTC）。基线时波形蛋白阳性CTC患者与无波形蛋白阳性CTC患者的基线PSA无显著差异（p = 0.33）。与无波形蛋白阳性CTC的患者相比，波形蛋白阳性CTC患者的OS显著缩短（中位生存期305天对453天，p = 0.0293）。基线时Ki67阳性CTC患者与无Ki67阳性CTC患者的基线PSA无显著差异（p = 0.228），但Ki67阳性CTC组的OS显著缩短（中位生存期512天对751天，p = 0.0091）。与基线相比，治疗后样本中波形蛋白或Ki67阳性CTC的相对比例未观察到变化。
结论
对mCRPC患者的CTC中波形蛋白和Ki67表达的分析可直接进行评估。波形蛋白和Ki67阳性CTC患者的生存结局较差。
转化研究方案
CEC-CTC（IDRCB2008-AOO585-50）和Petrus（NCT01786031）。
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