The Identification of Plasma Exosomal miR-423-3p as a Potential Predictive Biomarker for Prostate Cancer Castration-Resistance Development by Plasma Exosomal miRNA Sequencing
dc.contributor.author | Guo, T | |
dc.contributor.author | Wang, Y | |
dc.contributor.author | Jia, J | |
dc.contributor.author | Mao, X | |
dc.contributor.author | Stankiewicz, E | |
dc.contributor.author | Scandura, G | |
dc.contributor.author | Burke, E | |
dc.contributor.author | Xu, L | |
dc.contributor.author | Marzec, J | |
dc.contributor.author | Davies, CR | |
dc.contributor.author | Lu, JJ | |
dc.contributor.author | Rajan, P | |
dc.contributor.author | Grey, A | |
dc.contributor.author | Tipples, K | |
dc.contributor.author | Hines, J | |
dc.contributor.author | Kudahetti, S | |
dc.contributor.author | Oliver, T | |
dc.contributor.author | Powles, T | |
dc.contributor.author | Alifrangis, C | |
dc.contributor.author | Kohli, M | |
dc.contributor.author | Shaw, G | |
dc.contributor.author | Wang, W | |
dc.contributor.author | Feng, N | |
dc.contributor.author | Shamash, J | |
dc.contributor.author | Berney, D | |
dc.contributor.author | Wang, L | |
dc.contributor.author | Lu, Y-J | |
dc.date.accessioned | 2021-02-25T10:12:42Z | |
dc.date.available | 2020-11-30 | |
dc.date.available | 2021-02-25T10:12:42Z | |
dc.date.issued | 2021-01-07 | |
dc.identifier.issn | 2296-634X | |
dc.identifier.other | ARTN 602493 | |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/70501 | |
dc.description.abstract | Castration-resistant prostate cancer (CRPC) is the major cause of death from prostate cancer. Biomarkers to improve early detection and prediction of CRPC especially using non-invasive liquid biopsies could improve outcomes. Therefore, we investigated the plasma exosomal miRNAs associated with CRPC and their potential for development into non-invasive early detection biomarkers for resistance to treatment. RNA-sequencing, which generated approximately five million reads per patient, was performed to identify differentially expressed plasma exosomal miRNAs in 24 treatment-naive prostate cancer and 24 CRPC patients. RT-qPCR was used to confirm the differential expressions of six exosomal miRNAs, miR-423-3p, miR-320a, miR-99a-5p, miR-320d, miR-320b, and miR-150-5p (p = 7.3 × 10−8, 0.0020, 0.018, 0.0028, 0.0013, and 0.0058, respectively) firstly in a validation cohort of 108 treatment-naive prostate cancer and 42 CRPC patients. The most significant differentially expressed miRNA, miR-423-3p, was shown to be associated with CRPC with area under the ROC curve (AUC) = 0.784. Combining miR-423-3p with prostate-specific antigen (PSA) enhanced the prediction of CRPC (AUC = 0.908). A separate research center validation with 30 treatment-naive and 30 CRPC patients also confirmed the differential expression of miR-423-3p (p = 0.016). Finally, plasma exosomal miR-423-3p expression in CRPC patients was compared to 36 non-CRPC patients under androgen depletion therapy, which showed significantly higher expression in CRPC than treated non-CRPC patients (p < 0.0001) with AUC = 0.879 to predict CRPC with no difference between treatment-naive and treated non-CRPC patients. Therefore, our findings demonstrate that a number of plasma exosomal miRNAs are associated with CRPC and miR-423-3p may serve as a biomarker for early detection/prediction of castration-resistance. | en_US |
dc.publisher | Frontiers | en_US |
dc.relation.ispartof | FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY | |
dc.rights | This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. | |
dc.rights | Attribution 3.0 United States | * |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
dc.subject | prostate cancer | en_US |
dc.subject | castration-resistance development | en_US |
dc.subject | biomarker | en_US |
dc.subject | plasma exosome miRNA | en_US |
dc.subject | miR-423-3p | en_US |
dc.title | The Identification of Plasma Exosomal miR-423-3p as a Potential Predictive Biomarker for Prostate Cancer Castration-Resistance Development by Plasma Exosomal miRNA Sequencing | en_US |
dc.type | Article | en_US |
dc.rights.holder | © 2021 Guo, Wang, Jia, Mao, Stankiewicz, Scandura, Burke, Xu, Marzec, Davies, Lu, Rajan, Grey, Tipples, Hines, Kudahetti, Oliver, Powles, Alifrangis, Kohli, Shaw, Wang, Feng, Shamash, Berney, Wang and Lu. | |
dc.identifier.doi | 10.3389/fcell.2020.602493 | |
pubs.author-url | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000609131900001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 8 | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |
qmul.funder | Sam68 and hnRNPA2 in prostate cancer::Cancer Research UK | en_US |
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