{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T14:28:27Z","timestamp":1792506507909,"version":"4.5.0"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T00:00:00Z","timestamp":1626998400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T00:00:00Z","timestamp":1626998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81472383, 81772753, 81972419"],"award-info":[{"award-number":["81472383, 81772753, 81972419"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81502206"],"award-info":[{"award-number":["81502206"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2014A030313088, 2017A030313478"],"award-info":[{"award-number":["2014A030313088, 2017A030313478"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012245","name":"Science and Technology Planning Project of Guangdong Province","doi-asserted-by":"crossref","award":["2016A020215073"],"award-info":[{"award-number":["2016A020215073"]}],"id":[{"id":"10.13039\/501100012245","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010256","name":"Guangzhou Municipal Science and Technology Project","doi-asserted-by":"publisher","award":["201804010324"],"award-info":[{"award-number":["201804010324"]}],"id":[{"id":"10.13039\/501100010256","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["17ykzd21"],"award-info":[{"award-number":["17ykzd21"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Cancer"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The aim of this study was to identify a urine extracellular vesicle circular RNA (circRNA) classifier that could detect high-grade prostate cancer (PCa) of Grade Group (GG) 2 or greater. For this purpose, we used RNA sequencing to identify candidate circRNAs from urinary extracellular vesicles from 11 patients with high-grade PCa and 11 case-matched patients with benign prostatic hyperplasia. Using ddPCR in a training cohort (n\u2009=\u2009263), we built a urine extracellular vesicle circRNA classifier (Ccirc, containing <jats:italic>circPDLIM5, circSCAF8<\/jats:italic>, <jats:italic>circPLXDC2<\/jats:italic>, <jats:italic>circSCAMP1<\/jats:italic>, and <jats:italic>circCCNT2<\/jats:italic>), which was evaluated in two independent cohorts (n\u2009=\u2009497, n\u2009=\u2009505). Ccirc showed higher accuracy than two standard of care risk calculators (RCs) (PCPT-RC 2.0 and ERSPC-RC) in both the training cohort and the validation cohorts. In all three cohorts, this novel urine extracellular vesicle circRNA classifier plus RCs was statistically more predictive than RCs alone for predicting\u2009\u2265\u2009GG2 PCa. This assay, which does not require precollection digital rectal examination nor special handling, is repeatable, noninvasive, and can be easily implemented as part of the basic clinical workflow.<\/jats:p>","DOI":"10.1186\/s12943-021-01388-6","type":"journal-article","created":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T05:02:41Z","timestamp":1627016561000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["A urine extracellular vesicle circRNA classifier for detection of high-grade prostate cancer in patients with prostate-specific antigen 2\u201310\u00a0ng\/mL at initial biopsy"],"prefix":"10.1186","volume":"20","author":[{"given":"Ya-Di","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bang-Yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu-Mei","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang-Ming","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-Quan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Ming","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling-Xiao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Kui","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Min","family":"Rong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liao-Yuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,23]]},"reference":[{"issue":"6","key":"1388_CR1","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3322\/caac.21492","volume":"68","author":"F Bray","year":"2018","unstructured":"Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394\u2013424.","journal-title":"CA Cancer J Clin"},{"issue":"3","key":"1388_CR2","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1016\/j.eururo.2005.04.015","volume":"48","author":"AW Roddam","year":"2005","unstructured":"Roddam AW, Duffy MJ, Hamdy FC, et al. Use of prostate-specific antigen (PSA) isoforms for the detection of prostate cancer in men with a PSA level of 2\u201310 ng\/ml: systematic review and meta-analysis. Eur Urol. 2005;48(3):386\u201399.","journal-title":"Eur Urol"},{"issue":"1","key":"1388_CR3","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s12943-018-0852-7","volume":"17","author":"T Xu","year":"2018","unstructured":"Xu T, Lin CM, Cheng SQ, et al. Pathological bases and clinical impact of long noncoding RNAs in prostate cancer: a new budding star. Mol Cancer. 2018;17(1):103.","journal-title":"Mol Cancer"},{"issue":"4","key":"1388_CR4","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1016\/j.cell.2019.01.025","volume":"176","author":"S Chen","year":"2019","unstructured":"Chen S, Huang V, Xu X, et al. Widespread and Functional RNA Circularization in Localized Prostate Cancer. Cell. 2019;176(4):831-43.e22.","journal-title":"Cell"},{"issue":"1","key":"1388_CR5","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/s12943-019-1041-z","volume":"18","author":"Y Wang","year":"2019","unstructured":"Wang Y, Liu J, Ma J, et al. Exosomal circRNAs: biogenesis, effect and application in human diseases. Mol Cancer. 2019;18(1):116.","journal-title":"Mol Cancer"},{"issue":"6","key":"1388_CR6","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1016\/j.urology.2014.02.035","volume":"83","author":"DP Ankerst","year":"2014","unstructured":"Ankerst DP, Hoefler J, Bock S, et al. Prostate Cancer Prevention Trial risk calculator 2.0 for the prediction of low- vs high-grade prostate cancer. Urology. 2014;83(6):1362\u20137.","journal-title":"Urology"},{"issue":"5","key":"1388_CR7","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1111\/bju.13437","volume":"118","author":"RW Foley","year":"2016","unstructured":"Foley RW, Maweni RM, Gorman L, et al. European Randomised Study of Screening for Prostate Cancer (ERSPC) risk calculators significantly outperform the Prostate Cancer Prevention Trial (PCPT) 2.0 in the prediction of prostate cancer: a multi-institutional study. BJU Int. 2016;118(5):706\u201313.","journal-title":"BJU Int"},{"issue":"4","key":"1388_CR8","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1097\/PAS.0000000000000820","volume":"41","author":"JI Epstein","year":"2017","unstructured":"Epstein JI, Amin MB, Reuter VE, Humphrey PA. Contemporary Gleason Grading of Prostatic Carcinoma: An Update With Discussion on Practical Issues to Implement the 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol. 2017;41(4):e1\u20137.","journal-title":"Am J Surg Pathol"},{"issue":"4","key":"1388_CR9","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1016\/j.cell.2018.12.021","volume":"176","author":"JN Vo","year":"2019","unstructured":"Vo JN, Cieslik M, Zhang Y, et al. The Landscape of Circular RNA in Cancer. Cell. 2019;176(4):869-81.e813.","journal-title":"Cell"},{"issue":"1","key":"1388_CR10","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.eururo.2015.04.039","volume":"70","author":"SA Tomlins","year":"2016","unstructured":"Tomlins SA, Day JR, Lonigro RJ, et al. Urine TMPRSS2:ERG Plus PCA3 for Individualized Prostate Cancer Risk Assessment. Eur Urol. 2016;70(1):45\u201353.","journal-title":"Eur Urol"},{"key":"1388_CR11","doi-asserted-by":"crossref","unstructured":"Cucchiara V, Cooperberg MR, Dall\u2019Era M, et al. Genomic Markers in Prostate Cancer Decision Making. Eur Urol. 2018;73(4):572\u201382.","DOI":"10.1016\/j.eururo.2017.10.036"},{"issue":"11","key":"1388_CR12","doi-asserted-by":"publisher","first-page":"e509","DOI":"10.1016\/S1470-2045(12)70388-1","volume":"13","author":"HU Ahmed","year":"2012","unstructured":"Ahmed HU, Arya M, Freeman A, Emberton M. Do low-grade and low-volume prostate cancers bear the hallmarks of malignancy? Lancet Oncol. 2012;13(11):e509\u201317.","journal-title":"Lancet Oncol"}],"container-title":["Molecular Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12943-021-01388-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12943-021-01388-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12943-021-01388-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T05:03:43Z","timestamp":1627016623000},"score":1,"resource":{"primary":{"URL":"https:\/\/molecular-cancer.biomedcentral.com\/articles\/10.1186\/s12943-021-01388-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,23]]},"references-count":12,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1388"],"URL":"https:\/\/doi.org\/10.1186\/s12943-021-01388-6","relation":{},"ISSN":["1476-4598"],"issn-type":[{"value":"1476-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,23]]},"assertion":[{"value":"7 January 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Written informed consent for the biological studies was obtained from each patient involved in the study, and the study was approved by the Ethics Committees of the Third Affiliated Hospital of Sun Yat-sen University, Foshan First Municipal People\u2019s Hospital, the First Affiliated Hospital, University of South China, and the First Affiliated Hospital of Hainan\u00a0Medical College.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written consents for publication were obtained from all the patients involved in our study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"96"}}