Integrating extracellular vesicle and circulating cell-free DNA analysis using a single plasma aliquot improves the detection of HER2 positivity in breast cancer patients
Multi-analyte liquid biopsies represent an emerging opportunity for non-invasive cancer assessment. We developed ONCE (ONe Aliquot for Circulating Elements), an approach for the isolation of extracellular vesicles (EV) and cell-free DNA (cfDNA) from a single aliquot of blood. We assessed ONCE performance to classify HER2-positive early-stage breast cancer (BrCa) patients by combining EV-associated RNA (EV-RNA) and cfDNA signals on n=64 healthy donors (HD) and non-metastatic BrCa patients. Specifically, we isolated EV-enriched samples by a charge-based (CB) method and investigated EV-RNA and cfDNA by next-generation sequencing (NGS) and by digital droplet PCR (ddPCR). Sequencing of cfDNA and EV-RNA from HER2- and HER2+ patients demonstrated concordance with in situ molecular analyses of matched tissues. Combined analysis of the two circulating analytes by ddPCR showed increased sensitivity in ERBB2/HER2 detection compared to single nucleic acid components. Multi-analyte liquid biopsy prediction performance was comparable to tissue-based sequencing results from TCGA. Also, imaging flow cytometry analysis revealed HER2 protein on the surface of EV isolated from the HER2+ BrCa plasma, thus corroborating the potential relevance of studying EV as companion analyte to cfDNA. This data confirms the relevance of combining cfDNA and EV-RNA for HER2 cancer assessment and supports the ONCE as a valuable tool for multi-analytes liquid biopsies' clinical implementation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:2 |
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| Enthalten in: |
Journal of extracellular biology - 2(2023), 9 vom: 26. Sept. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mugoni, Vera [VerfasserIn] |
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| Links: |
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| Themen: |
Breast Cancer |
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| Anmerkungen: |
Date Revised 26.04.2024 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1002/jex2.108 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Multi-analyte liquid biopsies represent an emerging opportunity for non-invasive cancer assessment. We developed ONCE (ONe Aliquot for Circulating Elements), an approach for the isolation of extracellular vesicles (EV) and cell-free DNA (cfDNA) from a single aliquot of blood. We assessed ONCE performance to classify HER2-positive early-stage breast cancer (BrCa) patients by combining EV-associated RNA (EV-RNA) and cfDNA signals on n=64 healthy donors (HD) and non-metastatic BrCa patients. Specifically, we isolated EV-enriched samples by a charge-based (CB) method and investigated EV-RNA and cfDNA by next-generation sequencing (NGS) and by digital droplet PCR (ddPCR). Sequencing of cfDNA and EV-RNA from HER2- and HER2+ patients demonstrated concordance with in situ molecular analyses of matched tissues. Combined analysis of the two circulating analytes by ddPCR showed increased sensitivity in ERBB2/HER2 detection compared to single nucleic acid components. Multi-analyte liquid biopsy prediction performance was comparable to tissue-based sequencing results from TCGA. Also, imaging flow cytometry analysis revealed HER2 protein on the surface of EV isolated from the HER2+ BrCa plasma, thus corroborating the potential relevance of studying EV as companion analyte to cfDNA. This data confirms the relevance of combining cfDNA and EV-RNA for HER2 cancer assessment and supports the ONCE as a valuable tool for multi-analytes liquid biopsies' clinical implementation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Breast Cancer | |
| 650 | 4 | |a EV-RNA | |
| 650 | 4 | |a Extracellular Vesicles (EV) | |
| 650 | 4 | |a HER2 | |
| 650 | 4 | |a ImageStream | |
| 650 | 4 | |a ONCE approach | |
| 650 | 4 | |a cell-free DNA (cfDNA) | |
| 650 | 4 | |a ddPCR | |
| 700 | 1 | |a Ciani, Yari |e verfasserin |4 aut | |
| 700 | 1 | |a Quaini, Orsetta |e verfasserin |4 aut | |
| 700 | 1 | |a Tomasini, Simone |e verfasserin |4 aut | |
| 700 | 1 | |a Notarangelo, Michela |e verfasserin |4 aut | |
| 700 | 1 | |a Vannuccini, Federico |e verfasserin |4 aut | |
| 700 | 1 | |a Marinelli, Alessia |e verfasserin |4 aut | |
| 700 | 1 | |a Leonardi, Elena |e verfasserin |4 aut | |
| 700 | 1 | |a Pontalti, Stefano |e verfasserin |4 aut | |
| 700 | 1 | |a Martinelli, Angela |e verfasserin |4 aut | |
| 700 | 1 | |a Rossetto, Daniele |e verfasserin |4 aut | |
| 700 | 1 | |a Pesce, Isabella |e verfasserin |4 aut | |
| 700 | 1 | |a Mansy, Sheref S |e verfasserin |4 aut | |
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| 700 | 1 | |a Ferro, Antonella |e verfasserin |4 aut | |
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| 700 | 1 | |a Nardella, Caterina |e verfasserin |4 aut | |
| 700 | 1 | |a Demichelis, Francesca |e verfasserin |4 aut | |
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