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

Autor: Wong BS; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA., Shah SR; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Neurosurgery, Mayo Clinic, Jacksonville, FL, USA., Yankaskas CL; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA., Bajpai VK; Department of Chemical and Systems Biology, Stanford University, Stanford, CA, USA.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA., Wu PH; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA., Chin D; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA., Ifemembi B; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA., ReFaey K; Department of Neurosurgery, Mayo Clinic, Jacksonville, FL, USA., Schiapparelli P; Department of Neurosurgery, Mayo Clinic, Jacksonville, FL, USA., Zheng X; Department of Embryology, Carnegie Institution for Science, Baltimore, MD, USA., Martin SS; Marlene and Stewart Greenebaum National Cancer Institute Comprehensive Cancer Center, Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA., Fan CM; Department of Embryology, Carnegie Institution for Science, Baltimore, MD, USA., Quiñones-Hinojosa A; Department of Neurosurgery, Mayo Clinic, Jacksonville, FL, USA. Quinones-Hinojosa.Alfredo@mayo.edu., Konstantopoulos K; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA. konstant@jhu.edu.; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA. konstant@jhu.edu.; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA. konstant@jhu.edu.; Department of Oncology, Johns Hopkins University, Baltimore, MD, USA. konstant@jhu.edu.
Jazyk: angličtina
Zdroj: Nature biomedical engineering [Nat Biomed Eng] 2021 Jan; Vol. 5 (1), pp. 26-40. Date of Electronic Publication: 2020 Sep 28.
DOI: 10.1038/s41551-020-00621-9
Abstrakt: Clinical scores, molecular markers and cellular phenotypes have been used to predict the 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 correctly categorized five additional patients on the basis of survival prospectively. 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.
Databáze: MEDLINE
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