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

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 th...

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Autores principales: Wong, Bin Sheng, Shah, Sagar R., Yankaskas, Christopher L., Bajpai, Vivek K., Wu, Pei-Hsun, Chin, Deborah, Ifemembi, Brent, ReFaey, Karim, Schiapparelli, Paula, Zheng, Xiaobin, Martin, Stuart S., Fan, Chen-Ming, Quiñones-Hinojosa, Alfredo, Konstantopoulos, Konstantinos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855796/
https://www.ncbi.nlm.nih.gov/pubmed/32989283
http://dx.doi.org/10.1038/s41551-020-00621-9
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author Wong, Bin Sheng
Shah, Sagar R.
Yankaskas, Christopher L.
Bajpai, Vivek K.
Wu, Pei-Hsun
Chin, Deborah
Ifemembi, Brent
ReFaey, Karim
Schiapparelli, Paula
Zheng, Xiaobin
Martin, Stuart S.
Fan, Chen-Ming
Quiñones-Hinojosa, Alfredo
Konstantopoulos, Konstantinos
author_facet Wong, Bin Sheng
Shah, Sagar R.
Yankaskas, Christopher L.
Bajpai, Vivek K.
Wu, Pei-Hsun
Chin, Deborah
Ifemembi, Brent
ReFaey, Karim
Schiapparelli, Paula
Zheng, Xiaobin
Martin, Stuart S.
Fan, Chen-Ming
Quiñones-Hinojosa, Alfredo
Konstantopoulos, Konstantinos
author_sort Wong, Bin Sheng
collection PubMed
description 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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spelling pubmed-78557962021-03-28 A microfluidic cell-migration assay for the prediction of progression-free survival and recurrence time of patients with glioblastoma Wong, Bin Sheng Shah, Sagar R. Yankaskas, Christopher L. Bajpai, Vivek K. Wu, Pei-Hsun Chin, Deborah Ifemembi, Brent ReFaey, Karim Schiapparelli, Paula Zheng, Xiaobin Martin, Stuart S. Fan, Chen-Ming Quiñones-Hinojosa, Alfredo Konstantopoulos, Konstantinos Nat Biomed Eng Article 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. 2020-09-28 2021-01 /pmc/articles/PMC7855796/ /pubmed/32989283 http://dx.doi.org/10.1038/s41551-020-00621-9 Text en © The Author(s), under exclusive licence to Springer Nature Limited 2019 Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Wong, Bin Sheng
Shah, Sagar R.
Yankaskas, Christopher L.
Bajpai, Vivek K.
Wu, Pei-Hsun
Chin, Deborah
Ifemembi, Brent
ReFaey, Karim
Schiapparelli, Paula
Zheng, Xiaobin
Martin, Stuart S.
Fan, Chen-Ming
Quiñones-Hinojosa, Alfredo
Konstantopoulos, Konstantinos
A microfluidic cell-migration assay for the prediction of progression-free survival and recurrence time of patients with glioblastoma
title A microfluidic cell-migration assay for the prediction of progression-free survival and recurrence time of patients with glioblastoma
title_full A microfluidic cell-migration assay for the prediction of progression-free survival and recurrence time of patients with glioblastoma
title_fullStr A microfluidic cell-migration assay for the prediction of progression-free survival and recurrence time of patients with glioblastoma
title_full_unstemmed A microfluidic cell-migration assay for the prediction of progression-free survival and recurrence time of patients with glioblastoma
title_short A microfluidic cell-migration assay for the prediction of progression-free survival and recurrence time of patients with glioblastoma
title_sort microfluidic cell-migration assay for the prediction of progression-free survival and recurrence time of patients with glioblastoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855796/
https://www.ncbi.nlm.nih.gov/pubmed/32989283
http://dx.doi.org/10.1038/s41551-020-00621-9
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