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Single-cell microRNA sequencing of circulating tumour cells : a new tool for monitoring prostate cancer Jepson, Kevin Richard
Abstract
A major challenge in monitoring and managing metastatic cancer is the frequent inability to use invasive biopsies as a means of obtaining information regarding tumour progression. Circulating tumour cell (CTC) liquid biopsies—that is, collecting and analyzing CTCs from a blood sample—represent an opportunity for non-invasive cancer monitoring. The challenges of obtaining rare CTCs and sequencing single cell-amounts of miRNA have thus far made it impossible to accurately assess miRNA from CTCs. Here we present an integrated method combining negative-selection, high-throughput microscopy, micromanipulation, and microfluidics to measure the genome-wide expression of microRNAs (miRNAs) in single CTCs. Using our method, we generated single-cell miRNA expression profiles for 258 CTCs from 14 late-stage metastatic prostate cancer patients (mean 18 per patient). The total miRNA reads per cell was 27,423—accounting for 39% of aligned reads—while the mean detected miRNA species per cell was 155. Individual CTCs displayed significant interpatient heterogeneity, while intrapatient heterogeneity was comparatively low. Retrospective analysis of CTCs from castration-resistant prostate cancer patients provides preliminary evidence that miR-200b and miR-200a expression is negatively correlated with more aggressive tumour phenotypes; this demonstrates the potential of this method for monitoring and predicting disease progression in prostate cancer. This study establishes a method for obtaining single-cell miRNA profiles of CTCs, thereby enabling the ability to assess the important roles miRNAs play in cancer development, progression and response to treatment.
Item Metadata
| Title |
Single-cell microRNA sequencing of circulating tumour cells : a new tool for monitoring prostate cancer
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| Creator | |
| Publisher |
University of British Columbia
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| Date Issued |
2018
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| Description |
A major challenge in monitoring and managing metastatic cancer is the frequent inability to use invasive biopsies as a means of obtaining information regarding tumour progression. Circulating tumour cell (CTC) liquid biopsies—that is, collecting and analyzing CTCs from a blood sample—represent an opportunity for non-invasive cancer monitoring. The challenges of obtaining rare CTCs and sequencing single cell-amounts of miRNA have thus far made it impossible to accurately assess miRNA from CTCs. Here we present an integrated method combining negative-selection, high-throughput microscopy, micromanipulation, and microfluidics to measure the genome-wide expression of microRNAs (miRNAs) in single CTCs. Using our method, we generated single-cell miRNA expression profiles for 258 CTCs from 14 late-stage metastatic prostate cancer patients (mean 18 per patient). The total miRNA reads per cell was 27,423—accounting for 39% of aligned reads—while the mean detected miRNA species per cell was 155. Individual CTCs displayed significant interpatient heterogeneity, while intrapatient heterogeneity was comparatively low. Retrospective analysis of CTCs from castration-resistant prostate cancer patients provides preliminary evidence that miR-200b and miR-200a expression is negatively correlated with more aggressive tumour phenotypes; this demonstrates the potential of this method for monitoring and predicting disease progression in prostate cancer. This study establishes a method for obtaining single-cell miRNA profiles of CTCs, thereby enabling the ability to assess the important roles miRNAs play in cancer development, progression and response to treatment.
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| Genre | |
| Type | |
| Language |
eng
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| Date Available |
2019-04-30
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| Provider |
Vancouver : University of British Columbia Library
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| Rights |
Attribution-NonCommercial-NoDerivatives 4.0 International
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| DOI |
10.14288/1.0366134
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| URI | |
| Degree | |
| Program | |
| Affiliation | |
| Degree Grantor |
University of British Columbia
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| Graduation Date |
2018-09
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| Campus | |
| Scholarly Level |
Graduate
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| Rights URI | |
| Aggregated Source Repository |
DSpace
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Attribution-NonCommercial-NoDerivatives 4.0 International