Defining A Liquid Biopsy Profile of Circulating Tumor Cells and Oncosomes in Metastatic Colorectal Cancer for Clinical Utility
Metastatic colorectal cancer (mCRC) is characterized by its extensive disease heterogeneity, suggesting that individualized analysis could be vital to improving patient outcomes. As a minimally invasive approach, the liquid biopsy has the potential to longitudinally monitor heterogeneous analytes. C...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/19/4891 |
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| author | Sachin Narayan George Courcoubetis Jeremy Mason Amin Naghdloo Drahomír Kolenčík Scott D. Patterson Peter Kuhn Stephanie N. Shishido |
| author_facet | Sachin Narayan George Courcoubetis Jeremy Mason Amin Naghdloo Drahomír Kolenčík Scott D. Patterson Peter Kuhn Stephanie N. Shishido |
| author_sort | Sachin Narayan |
| collection | DOAJ |
| description | Metastatic colorectal cancer (mCRC) is characterized by its extensive disease heterogeneity, suggesting that individualized analysis could be vital to improving patient outcomes. As a minimally invasive approach, the liquid biopsy has the potential to longitudinally monitor heterogeneous analytes. Current platforms primarily utilize enrichment-based approaches for epithelial-derived circulating tumor cells (CTC), but this subtype is infrequent in the peripheral blood (PB) of mCRC patients, leading to the liquid biopsy’s relative disuse in this cancer type. In this study, we evaluated 18 PB samples from 10 mCRC patients using the unbiased high-definition single-cell assay (HDSCA). We first employed a rare-event (Landscape) immunofluorescence (IF) protocol, which captured a heterogenous CTC and oncosome population, the likes of which was not observed across 50 normal donor (ND) samples. Subsequent analysis was conducted using a colorectal-targeted IF protocol to assess the frequency of CDX2-expressing CTCs and oncosomes. A multi-assay clustering analysis isolated morphologically distinct subtypes across the two IF stains, demonstrating the value of applying an unbiased single-cell approach to multiple assays in tandem. Rare-event enumerations at a single timepoint and the variation of these events over time correlated with progression-free survival. This study supports the clinical utility of an unbiased approach to interrogating the liquid biopsy in mCRC, representing the heterogeneity within the CTC classification and warranting the further molecular characterization of the rare-event analytes with clinical promise. |
| first_indexed | 2024-03-09T21:55:50Z |
| format | Article |
| id | doaj.art-7ef97f5cbce446768281ee80a8e7592e |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T21:55:50Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-7ef97f5cbce446768281ee80a8e7592e2023-11-23T19:58:18ZengMDPI AGCancers2072-66942022-10-011419489110.3390/cancers14194891Defining A Liquid Biopsy Profile of Circulating Tumor Cells and Oncosomes in Metastatic Colorectal Cancer for Clinical UtilitySachin Narayan0George Courcoubetis1Jeremy Mason2Amin Naghdloo3Drahomír Kolenčík4Scott D. Patterson5Peter Kuhn6Stephanie N. Shishido7Michelson Center for Convergent Bioscience, Convergent Science Institute in Cancer, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA 90089, USAMichelson Center for Convergent Bioscience, Convergent Science Institute in Cancer, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA 90089, USAMichelson Center for Convergent Bioscience, Convergent Science Institute in Cancer, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA 90089, USAMichelson Center for Convergent Bioscience, Convergent Science Institute in Cancer, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA 90089, USABiomedical Center, Faculty of Medicine in Pilsen, Charles University, 32300 Pilsen, Czech RepublicGilead Sciences, Inc., Lakeside Drive, Foster City, CA 94404, USAMichelson Center for Convergent Bioscience, Convergent Science Institute in Cancer, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA 90089, USAMichelson Center for Convergent Bioscience, Convergent Science Institute in Cancer, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA 90089, USAMetastatic colorectal cancer (mCRC) is characterized by its extensive disease heterogeneity, suggesting that individualized analysis could be vital to improving patient outcomes. As a minimally invasive approach, the liquid biopsy has the potential to longitudinally monitor heterogeneous analytes. Current platforms primarily utilize enrichment-based approaches for epithelial-derived circulating tumor cells (CTC), but this subtype is infrequent in the peripheral blood (PB) of mCRC patients, leading to the liquid biopsy’s relative disuse in this cancer type. In this study, we evaluated 18 PB samples from 10 mCRC patients using the unbiased high-definition single-cell assay (HDSCA). We first employed a rare-event (Landscape) immunofluorescence (IF) protocol, which captured a heterogenous CTC and oncosome population, the likes of which was not observed across 50 normal donor (ND) samples. Subsequent analysis was conducted using a colorectal-targeted IF protocol to assess the frequency of CDX2-expressing CTCs and oncosomes. A multi-assay clustering analysis isolated morphologically distinct subtypes across the two IF stains, demonstrating the value of applying an unbiased single-cell approach to multiple assays in tandem. Rare-event enumerations at a single timepoint and the variation of these events over time correlated with progression-free survival. This study supports the clinical utility of an unbiased approach to interrogating the liquid biopsy in mCRC, representing the heterogeneity within the CTC classification and warranting the further molecular characterization of the rare-event analytes with clinical promise.https://www.mdpi.com/2072-6694/14/19/4891liquid biopsyrare cellcirculating tumor cellsoncosomescolorectal cancerheterogeneity |
| spellingShingle | Sachin Narayan George Courcoubetis Jeremy Mason Amin Naghdloo Drahomír Kolenčík Scott D. Patterson Peter Kuhn Stephanie N. Shishido Defining A Liquid Biopsy Profile of Circulating Tumor Cells and Oncosomes in Metastatic Colorectal Cancer for Clinical Utility Cancers liquid biopsy rare cell circulating tumor cells oncosomes colorectal cancer heterogeneity |
| title | Defining A Liquid Biopsy Profile of Circulating Tumor Cells and Oncosomes in Metastatic Colorectal Cancer for Clinical Utility |
| title_full | Defining A Liquid Biopsy Profile of Circulating Tumor Cells and Oncosomes in Metastatic Colorectal Cancer for Clinical Utility |
| title_fullStr | Defining A Liquid Biopsy Profile of Circulating Tumor Cells and Oncosomes in Metastatic Colorectal Cancer for Clinical Utility |
| title_full_unstemmed | Defining A Liquid Biopsy Profile of Circulating Tumor Cells and Oncosomes in Metastatic Colorectal Cancer for Clinical Utility |
| title_short | Defining A Liquid Biopsy Profile of Circulating Tumor Cells and Oncosomes in Metastatic Colorectal Cancer for Clinical Utility |
| title_sort | defining a liquid biopsy profile of circulating tumor cells and oncosomes in metastatic colorectal cancer for clinical utility |
| topic | liquid biopsy rare cell circulating tumor cells oncosomes colorectal cancer heterogeneity |
| url | https://www.mdpi.com/2072-6694/14/19/4891 |
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