A microfluidic cell-migration assay for the prediction of progression-free survival and recurrence time of patients with glioblastoma.

A microfluidic cell-migration assay for the prediction of progression-free survival and recurrence time of patients with glioblastoma.
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用于预测胶质母细胞瘤患者的无进展生存时间和复发时间的微流体细胞迁移测定。

DOI:
10.1038/s41551-020-00621-9
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发表时间:
2021-01
影响因子:
28.1
通讯作者:
Konstantopoulos K
Konstantopoulos K
中科院分区:
工程技术1区
文献类型:
--
作者:
Wong BS;Shah SR;Yankaskas CL;Bajpai VK;Wu PH;Chin D;Ifemembi B;ReFaey K;Schiapparelli P;Zheng X;Martin SS;Fan CM;Quiñones-Hinojosa A;Konstantopoulos K

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临床评分、分子标志物和细胞表型已被用于预测胶质母细胞瘤患者的临床结果。然而,它们的临床应用受到了混杂因素的阻碍,如患者的共病,肿瘤分子和细胞标志物的异质性,以及高通量单细胞分析的复杂性和成本。在这里,我们展示了一种用于量化细胞迁移和增殖的微流控分析方法,可以根据无进展生存期对胶质母细胞瘤患者进行分类。我们用综合分数量化了原代胶质母细胞瘤细胞的增殖能力(通过蛋白质生物标记物Ki-67)和挤压通过微流体通道的能力,模拟了脑实质中紧密的血管周围管道和白质束的某些方面。该分析根据无进展生存(短期或长期)对28名患者进行了回顾性分类,准确率为86%,预测了复发时间,并根据生存情况前瞻性地对另外5名患者进行了分类。对高运动性细胞的RNA测序显示了与预后不良相关的差异表达基因。我们的发现表明,细胞迁移和增殖水平可以预测患者特定的临床结果。
Clinical scores, molecular markers and cellular phenotypes have been used to predict clinical outcomes of patients with glioblastoma. However, their clinical use has been hampered by confounders such as patient co-morbidities, by the tumoral heterogeneity of molecular and cellular markers, and by the complexity and cost of high-throughput single-cell analysis. Here, we show that a microfluidic assay for the quantification of cell migration and proliferation can categorize patients with glioblastoma according to progression-free survival. We quantified with a composite score the ability of primary glioblastoma cells to proliferate (via the protein biomarker Ki-67) and to squeeze through microfluidic channels, mimicking aspects of the tight perivascular conduits and white-matter tracts in brain parenchyma. The assay retrospectively categorized 28 patients according to progression-free survival (short-term or long-term) with an accuracy of 86%, predicted time to recurrence, and prospectively categorized five additional patients on the basis of survival. RNA sequencing of the highly motile cells revealed differentially expressed genes that correlated with poor prognosis. Our findings suggest that cell-migration and proliferation levels can predict patient-specific clinical outcomes.
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