Validation of potential RNA biomarkers for prostate cancer diagnosis and monitoring in plasma and urinary extracellular vesicles

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dc.contributor.authorBrokāne, Agnese
dc.contributor.authorBajo-Santos, Cristina
dc.contributor.authorZayakin, Pawel
dc.contributor.authorBelovs, Alberts
dc.contributor.authorJansons, Juris
dc.contributor.authorLietuvietis, Vilnis
dc.contributor.authorMartens-Uzunova, Elena S.
dc.contributor.authorJenster, Guido W.
dc.contributor.authorLinē, Aija
dc.contributor.institutionRīga Stradiņš University
dc.date.accessioned2024-02-29T10:20:01Z
dc.date.available2024-02-29T10:20:01Z
dc.date.issued2023-11-30
dc.descriptionPublisher Copyright: Copyright © 2023 Brokāne, Bajo-Santos, Zayakin, Belovs, Jansons, Lietuvietis, Martens-Uzunova, Jenster and Linē.
dc.description.abstractIntroduction: Prostate cancer (PCa), one of the most prevalent malignancies affecting men worldwide, presents significant challenges in terms of early detection, risk stratification, and active surveillance. In recent years, liquid biopsies have emerged as a promising non-invasive approach to complement or even replace traditional tissue biopsies. Extracellular vesicles (EVs), nanosized membranous structures released by various cells into body fluids, have gained substantial attention as a source of cancer biomarkers due to their ability to encapsulate and transport a wide range of biological molecules, including RNA. In this study, we aimed to validate 15 potential RNA biomarkers, identified in a previous EV RNA sequencing study, using droplet digital PCR. Methods: The candidate biomarkers were tested in plasma and urinary EVs collected before and after radical prostatectomy from 30 PCa patients and their diagnostic potential was evaluated in a test cohort consisting of 20 benign prostate hyperplasia (BPH) and 20 PCa patients’ plasma and urinary EVs. Next, the results were validated in an independent cohort of plasma EVs from 31 PCa and 31 BPH patients. Results: We found that the levels of NKX3-1 (p = 0.0008) in plasma EVs, and tRF-Phe-GAA-3b (p < 0.0001) tRF-Lys-CTT-5c (p < 0.0327), piR-28004 (p = 0.0081) and miR-375-3p (p < 0.0001) in urinary EVs significantly decreased after radical prostatectomy suggesting that the main tissue source of these RNAs is prostate and/or PCa. Two mRNA biomarkers—GLO1 and NKX3-1 showed promising diagnostic potential in distinguishing between PCa and BPH with AUC of 0.68 and 0.82, respectively, in the test cohort and AUC of 0.73 and 0.65, respectively, in the validation cohort, when tested in plasma EVs. Combining these markers in a biomarker model yielded AUC of 0.85 and 0.71 in the test and validation cohorts, respectively. Although the PSA levels in the blood could not distinguish PCa from BPH in our cohort, adding PSA to the mRNA biomarker model increased AUC from 0.71 to 0.76. Conclusion: This study identified two novel EV-enclosed RNA biomarkers–NKX3-1 and GLO1–for the detection of PCa, and highlights the complementary nature of GLO1, NKX3-1 and PSA as combined biomarkers in liquid biopsies of PCa.en
dc.description.statusPeer reviewed
dc.format.extent15
dc.format.extent3115911
dc.identifier.citationBrokāne, A, Bajo-Santos, C, Zayakin, P, Belovs, A, Jansons, J, Lietuvietis, V, Martens-Uzunova, E S, Jenster, G W & Linē, A 2023, 'Validation of potential RNA biomarkers for prostate cancer diagnosis and monitoring in plasma and urinary extracellular vesicles', Frontiers in Molecular Biosciences, vol. 10, 1279854, pp. 01-15. https://doi.org/10.3389/fmolb.2023.1279854
dc.identifier.doi10.3389/fmolb.2023.1279854
dc.identifier.issn2296-889X
dc.identifier.urihttps://dspace.rsu.lv/jspui/handle/123456789/15350
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85179931814&partnerID=8YFLogxK
dc.language.isoeng
dc.relation.ispartofFrontiers in Molecular Biosciences
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectdroplet digital PCR
dc.subjectextracellular vesicles
dc.subjectliquid biopsies
dc.subjectprostate cancer
dc.subjectRNA biomarkers
dc.subject3.1 Basic medicine
dc.subject3.2 Clinical medicine
dc.subject1.1. Scientific article indexed in Web of Science and/or Scopus database
dc.subjectBiochemistry
dc.subjectMolecular Biology
dc.subjectBiochemistry, Genetics and Molecular Biology (miscellaneous)
dc.subjectSDG 3 - Good Health and Well-being
dc.titleValidation of potential RNA biomarkers for prostate cancer diagnosis and monitoring in plasma and urinary extracellular vesiclesen
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article

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