{"doi":"10.3389/fcell.2020.602493","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","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.","journal":"Frontiers in Cell and Developmental Biology","year":2021,"id":153992,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":65,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9549,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":653043,"name":"Yang Wang","orcid":"0000-0002-1849-9319","position":1,"is_corresponding":false},{"id":434291,"name":"Jing Jia","orcid":"0000-0002-5840-8653","position":2,"is_corresponding":false},{"id":653044,"name":"Xueying Mao","orcid":"0000-0001-6306-7534","position":3,"is_corresponding":false},{"id":653045,"name":"Elzbieta Stankiewicz","orcid":"0000-0003-0812-4086","position":4,"is_corresponding":false},{"id":653046,"name":"Glenda Scandura","orcid":"0000-0002-0537-5894","position":5,"is_corresponding":false},{"id":654150,"name":"Edwina Burke","orcid":null,"position":6,"is_corresponding":false},{"id":523802,"name":"Lei Xu","orcid":"0000-0002-8499-0448","position":7,"is_corresponding":false},{"id":653047,"name":"Jacek Marzec","orcid":"0000-0001-6577-8866","position":8,"is_corresponding":false},{"id":654151,"name":"Caitlin R. Davies","orcid":null,"position":9,"is_corresponding":false},{"id":448864,"name":"Jiaying Lu","orcid":"0000-0003-0927-0042","position":10,"is_corresponding":false},{"id":653048,"name":"Prabhakar Rajan","orcid":"0000-0001-8064-9878","position":11,"is_corresponding":false},{"id":453076,"name":"Alistair Grey","orcid":"0000-0001-6017-8546","position":12,"is_corresponding":false},{"id":654152,"name":"Karen Tipples","orcid":null,"position":13,"is_corresponding":false},{"id":653049,"name":"John Hines","orcid":"0000-0002-5041-7694","position":14,"is_corresponding":false},{"id":654153,"name":"Sakunthala C. Kudahetti","orcid":null,"position":15,"is_corresponding":false},{"id":610006,"name":"R.T.D. Oliver","orcid":"0000-0002-7879-8943","position":16,"is_corresponding":false},{"id":235728,"name":"Thomas Powles","orcid":"0000-0001-7760-4724","position":17,"is_corresponding":false},{"id":653050,"name":"Constantine Alifrangis","orcid":"0000-0002-5876-6696","position":18,"is_corresponding":false},{"id":263983,"name":"Manish Kohli","orcid":"0000-0002-9735-6614","position":19,"is_corresponding":false},{"id":653051,"name":"Greg Shaw","orcid":"0000-0003-3480-2100","position":20,"is_corresponding":false},{"id":387923,"name":"Wen Wang","orcid":"0000-0003-2473-7210","position":21,"is_corresponding":false},{"id":653052,"name":"Ninghan Feng","orcid":"0000-0002-0892-6102","position":22,"is_corresponding":false},{"id":654154,"name":"Jonathan Shamash","orcid":null,"position":23,"is_corresponding":false},{"id":13255,"name":"Daniel M. 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