Longitudinal Multi-Parametric Liquid Biopsy Approach Identifies Unique Features of Circulating Tumor Cell, Extracellular Vesicle, and Cell-Free DNA Characterization for Disease Monitoring in Metastatic Breast Cancer Patients
Dynamics of mRNA from circulating tumor cells (CTCs), mRNA from extracellular vesicles (EVs), and cell-free DNA (cfDNA) were assessed to examine the relevance of a longitudinal multi-parametric liquid biopsy strategy. Eighteen milliliters of blood was drawn from 27 hormone receptor-positive and huma...
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MDPI AG
2021-01-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/2/212 |
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| author | Corinna Keup Vinay Suryaprakash Markus Storbeck Oliver Hoffmann Rainer Kimmig Sabine Kasimir-Bauer |
| author_facet | Corinna Keup Vinay Suryaprakash Markus Storbeck Oliver Hoffmann Rainer Kimmig Sabine Kasimir-Bauer |
| author_sort | Corinna Keup |
| collection | DOAJ |
| description | Dynamics of mRNA from circulating tumor cells (CTCs), mRNA from extracellular vesicles (EVs), and cell-free DNA (cfDNA) were assessed to examine the relevance of a longitudinal multi-parametric liquid biopsy strategy. Eighteen milliliters of blood was drawn from 27 hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) patients at disease progression and at two subsequent radiologic staging time points. CTC mRNA and EV mRNA were analyzed using multi-marker qPCR, and cfDNA was analyzed using targeted next-generation sequencing (NGS). The presence of <i>ERBB2</i> or <i>ERBB3</i> overexpression signals in CTCs significantly correlated with disease progression (87% specificity, 36% sensitivity, <i>p</i>-value = 0.023), and the presence of either <i>ERBB3</i> signals in CTCs or EVs or cfDNA variants in <i>ERBB3</i> also showed a significant association with progressive MBC. Fluctuations during treatment were detected in the EV fraction with the appearance of hitherto undetected <i>ERCC1</i> signals correlating with progressive disease (97% specificity, 18% sensitivity, <i>p</i>-value = 0.030). Allele frequency development of <i>ESR1</i> and <i>PIK3CA</i> variants detected at subsequent staging time points could be used as a predictor for therapy success and, importantly, might help guide therapy decisions. The three analytes, each with their own unique features for disease monitoring, were shown to be complementary, underlining the usefulness of the longitudinal multi-parametric liquid biopsy approach. |
| first_indexed | 2024-03-09T04:04:55Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T04:04:55Z |
| publishDate | 2021-01-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-b9ad432d38224a46a0e32de57d31d8412023-12-03T14:08:48ZengMDPI AGCells2073-44092021-01-0110221210.3390/cells10020212Longitudinal Multi-Parametric Liquid Biopsy Approach Identifies Unique Features of Circulating Tumor Cell, Extracellular Vesicle, and Cell-Free DNA Characterization for Disease Monitoring in Metastatic Breast Cancer PatientsCorinna Keup0Vinay Suryaprakash1Markus Storbeck2Oliver Hoffmann3Rainer Kimmig4Sabine Kasimir-Bauer5Department of Gynecology and Obstetrics, University Hospital of Essen, 45122 Essen, GermanyQIAGEN GmbH, 40724 Hilden, GermanyQIAGEN GmbH, 40724 Hilden, GermanyDepartment of Gynecology and Obstetrics, University Hospital of Essen, 45122 Essen, GermanyDepartment of Gynecology and Obstetrics, University Hospital of Essen, 45122 Essen, GermanyDepartment of Gynecology and Obstetrics, University Hospital of Essen, 45122 Essen, GermanyDynamics of mRNA from circulating tumor cells (CTCs), mRNA from extracellular vesicles (EVs), and cell-free DNA (cfDNA) were assessed to examine the relevance of a longitudinal multi-parametric liquid biopsy strategy. Eighteen milliliters of blood was drawn from 27 hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) patients at disease progression and at two subsequent radiologic staging time points. CTC mRNA and EV mRNA were analyzed using multi-marker qPCR, and cfDNA was analyzed using targeted next-generation sequencing (NGS). The presence of <i>ERBB2</i> or <i>ERBB3</i> overexpression signals in CTCs significantly correlated with disease progression (87% specificity, 36% sensitivity, <i>p</i>-value = 0.023), and the presence of either <i>ERBB3</i> signals in CTCs or EVs or cfDNA variants in <i>ERBB3</i> also showed a significant association with progressive MBC. Fluctuations during treatment were detected in the EV fraction with the appearance of hitherto undetected <i>ERCC1</i> signals correlating with progressive disease (97% specificity, 18% sensitivity, <i>p</i>-value = 0.030). Allele frequency development of <i>ESR1</i> and <i>PIK3CA</i> variants detected at subsequent staging time points could be used as a predictor for therapy success and, importantly, might help guide therapy decisions. The three analytes, each with their own unique features for disease monitoring, were shown to be complementary, underlining the usefulness of the longitudinal multi-parametric liquid biopsy approach.https://www.mdpi.com/2073-4409/10/2/212multi-parametricmulti-modalmulti-analytefollow-upserial samplinggene expression |
| spellingShingle | Corinna Keup Vinay Suryaprakash Markus Storbeck Oliver Hoffmann Rainer Kimmig Sabine Kasimir-Bauer Longitudinal Multi-Parametric Liquid Biopsy Approach Identifies Unique Features of Circulating Tumor Cell, Extracellular Vesicle, and Cell-Free DNA Characterization for Disease Monitoring in Metastatic Breast Cancer Patients Cells multi-parametric multi-modal multi-analyte follow-up serial sampling gene expression |
| title | Longitudinal Multi-Parametric Liquid Biopsy Approach Identifies Unique Features of Circulating Tumor Cell, Extracellular Vesicle, and Cell-Free DNA Characterization for Disease Monitoring in Metastatic Breast Cancer Patients |
| title_full | Longitudinal Multi-Parametric Liquid Biopsy Approach Identifies Unique Features of Circulating Tumor Cell, Extracellular Vesicle, and Cell-Free DNA Characterization for Disease Monitoring in Metastatic Breast Cancer Patients |
| title_fullStr | Longitudinal Multi-Parametric Liquid Biopsy Approach Identifies Unique Features of Circulating Tumor Cell, Extracellular Vesicle, and Cell-Free DNA Characterization for Disease Monitoring in Metastatic Breast Cancer Patients |
| title_full_unstemmed | Longitudinal Multi-Parametric Liquid Biopsy Approach Identifies Unique Features of Circulating Tumor Cell, Extracellular Vesicle, and Cell-Free DNA Characterization for Disease Monitoring in Metastatic Breast Cancer Patients |
| title_short | Longitudinal Multi-Parametric Liquid Biopsy Approach Identifies Unique Features of Circulating Tumor Cell, Extracellular Vesicle, and Cell-Free DNA Characterization for Disease Monitoring in Metastatic Breast Cancer Patients |
| title_sort | longitudinal multi parametric liquid biopsy approach identifies unique features of circulating tumor cell extracellular vesicle and cell free dna characterization for disease monitoring in metastatic breast cancer patients |
| topic | multi-parametric multi-modal multi-analyte follow-up serial sampling gene expression |
| url | https://www.mdpi.com/2073-4409/10/2/212 |
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