Extracellular Vesicles—A Source of RNA Biomarkers for the Detection of Breast Cancer in Liquid Biopsies

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dc.contributor.authorZayakin, Pawel
dc.contributor.authorSadovska, Lilite
dc.contributor.authorEglītis, Kristaps
dc.contributor.authorRomanchikova, Nadezhda
dc.contributor.authorRadoviča-Spalviņa, Ilze
dc.contributor.authorEndzeliņš, Edgars
dc.contributor.authorLiepniece-Karele, Inta
dc.contributor.authorEglītis, Jānis
dc.contributor.authorLinē, Aija
dc.contributor.institutionDepartment of Pathology
dc.date.accessioned2024-02-27T06:20:03Z
dc.date.available2024-02-27T06:20:03Z
dc.date.issued2023-09
dc.descriptionPublisher Copyright: © 2023 by the authors.
dc.description.abstractOver the past decade, extracellular vesicles (EVs) have emerged as a promising source of cancer-derived RNAs for liquid biopsies. However, blood contains a pool of heterogeneous EVs released by a variety of cell types, making the identification of cancer RNA biomarkers challenging. Here, we performed deep sequencing of plasma EV RNA cargo in 32 patients with locally advanced breast cancer (BC) at diagnosis and 7 days after breast surgery and in 30 cancer-free healthy controls (HCs). To identify BC-derived RNA biomarkers, we searched for RNAs that had higher levels in BC EVs at the time of diagnosis compared with HCs and decreased after surgery. Data analysis showed that the fractions of miRNAs, snRNAs, snoRNAs, and tRFs were increased, but the fraction of lncRNAs was decreased in BC EVs as compared to HCs. BC-derived biomarker candidates were identified across various RNA biotypes. Considered individually, they had very high specificity but moderate sensitivity for the detection of BC, whereas a biomarker model composed of eight RNAs: SNORD3H, SNORD1C, SNORA74D, miR-224-5p, piR-32949, lnc-IFT-122-2, lnc-C9orf50-4, and lnc-FAM122C-3 was able to distinguish BC from HC EVs with an AUC of 0.902 (95% CI = 0.872–0.931, p = 3.4 × 10−9) in leave-one-out cross-validation. Furthermore, a number of RNA biomarkers were correlated with the ER and HER2 expression and additional biomarker models were created to predict hormone receptor and HER2 status. Overall, this study demonstrated that the RNA composition of plasma EVs is altered in BC patients and that they contain cancer-derived RNA biomarkers that can be used for BC detection and monitoring using liquid biopsies.en
dc.description.statusPeer reviewed
dc.format.extent18
dc.format.extent21623752
dc.identifier.citationZayakin, P, Sadovska, L, Eglītis, K, Romanchikova, N, Radoviča-Spalviņa, I, Endzeliņš, E, Liepniece-Karele, I, Eglītis, J & Linē, A 2023, 'Extracellular Vesicles—A Source of RNA Biomarkers for the Detection of Breast Cancer in Liquid Biopsies', Cancers, vol. 15, no. 17, 4329, pp. 1-18. https://doi.org/10.3390/cancers15174329
dc.identifier.doi10.3390/cancers15174329
dc.identifier.issn2072-6694
dc.identifier.urihttps://dspace.rsu.lv/jspui/handle/123456789/15335
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85170220611&partnerID=8YFLogxK
dc.language.isoeng
dc.relation.ispartofCancers
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectbreast cancer
dc.subjectdiagnostic biomarker
dc.subjectextracellular vesicles
dc.subjectliquid biopsy
dc.subjectmitochondria-derived EVs
dc.subjectRNA sequencing
dc.subjectsnoRNA
dc.subject3.1 Basic medicine
dc.subject1.1. Scientific article indexed in Web of Science and/or Scopus database
dc.subjectOncology
dc.subjectCancer Research
dc.subjectSDG 3 - Good Health and Well-being
dc.titleExtracellular Vesicles—A Source of RNA Biomarkers for the Detection of Breast Cancer in Liquid Biopsiesen
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article

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