Integrating extracellular vesicle and circulating cell-free DNA analysis using a single plasma aliquot improves the detection of HER2 positivity in breast cancer patients.

Autor: Mugoni V; Department of Cellular, Computational and Integrative Biology University of Trento Trento Italy., Ciani Y; Department of Cellular, Computational and Integrative Biology University of Trento Trento Italy., Quaini O; Department of Cellular, Computational and Integrative Biology University of Trento Trento Italy., Tomasini S; Department of Cellular, Computational and Integrative Biology University of Trento Trento Italy., Notarangelo M; Department of Cellular, Computational and Integrative Biology University of Trento Trento Italy., Vannuccini F; Department of Cellular, Computational and Integrative Biology University of Trento Trento Italy., Marinelli A; Department of Cellular, Computational and Integrative Biology University of Trento Trento Italy., Leonardi E; Unit of Surgical Pathology, Santa Chiara Hospital, APSS Trento Italy., Pontalti S; Department of Medical Oncology Santa Chiara Hospital, APSS Trento Italy., Martinelli A; Department of Cellular, Computational and Integrative Biology University of Trento Trento Italy., Rossetto D; Department of Cellular, Computational and Integrative Biology University of Trento Trento Italy., Pesce I; Department of Cellular, Computational and Integrative Biology University of Trento Trento Italy., Mansy SS; Department of Cellular, Computational and Integrative Biology University of Trento Trento Italy., Barbareschi M; Unit of Surgical Pathology, Santa Chiara Hospital, APSS Trento Italy., Ferro A; Department of Medical Oncology Santa Chiara Hospital, APSS Trento Italy., Caffo O; Department of Medical Oncology Santa Chiara Hospital, APSS Trento Italy., Attard G; University College London Cancer Institute London UK., Di Vizio D; Department of Surgery, Division of Cancer Biology and Therapeutics Cedars-Sinai Medical Center Los Angeles California USA., D'Agostino VG; Department of Cellular, Computational and Integrative Biology University of Trento Trento Italy., Nardella C; Department of Cellular, Computational and Integrative Biology University of Trento Trento Italy., Demichelis F; Department of Cellular, Computational and Integrative Biology University of Trento Trento Italy.
Jazyk: angličtina
Zdroj: Journal of extracellular biology [J Extracell Biol] 2023 Sep; Vol. 2 (9), pp. e108. Date of Electronic Publication: 2023 Sep 25.
DOI: 10.1002/jex2.108
Abstrakt: 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 ONCE as a valuable tool for multi-analytes liquid biopsies' clinical implementation.
Competing Interests: An Italian Patent Application no. 102021000027854 was filed on October 29th, 2021, on the ONCE methodology (authors involved are VM, YC, OQ, MN, VGD, CN, FD). All remaining authors have declared no conflicts of interest.
(© 2023 The Authors. Journal of Extracellular Biology published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje