{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T11:05:08Z","timestamp":1782471908735,"version":"3.54.5"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81572935"],"award-info":[{"award-number":["81572935"]}],"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":["81872396"],"award-info":[{"award-number":["81872396"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The accuracy of prostate-specific antigen or clinical examination in prostate cancer (PCa) screening is in question, and circulating microRNAs (miRNAs) can be alternatives to PCa diagnosis. However, recent circulating miRNA biomarkers either are identified upon small sample sizes or cannot have robust diagnostic performance in every aspect of performance indicators. These may decrease applicability of potential biomarkers for the early detection of PCa. We reviewed recent studies on blood-derived miRNAs for prostate cancer diagnosis and carried out a large case study to understand whether circulating miRNA pairs, rather than single circulating miRNAs, could contribute to a more robust diagnostic model to significantly improve PCa diagnosis. We used 1231 high-throughput miRNA-profiled serum samples from two cohorts to design and verify a model based on class separability miRNA pairs (cs-miRPs). The pairwise model was composed of five circulating miRNAs coupled to miR-5100 and miR-1290 (i.e. five miRNA pairs, 5-cs-miRPs), reaching approximately 99% diagnostic performance in almost all indicators (sensitivity\u2009=\u200998.96%, specificity\u2009=\u2009100%, accuracy\u2009=\u200999.17%, PPV\u2009=\u2009100%, NPV\u2009=\u200996.15%) shown by a test set (n\u2009=\u2009484: PCa\u2009=\u2009384, negative prostate biopsies\u2009=\u2009100). The nearly 99% diagnostic performance was also verified by an additional validation set (n\u2009=\u2009140: PCa\u2009=\u200940, healthy controls\u2009=\u2009100). Overall, the 5-cs-miRP model had 1 false positive and 7 false negatives among the 1231 serum samples and was superior to a recent 2-miRNA model (so far the best for PCa diagnosis) with 18 false positives and 80 false negatives. The present large case study demonstrated that circulating miRNA pairs could potentially bring more benefits to PCa early diagnosis for clinical practice.<\/jats:p>","DOI":"10.1093\/bib\/bbaa111","type":"journal-article","created":{"date-parts":[[2020,5,15]],"date-time":"2020-05-15T16:52:29Z","timestamp":1589561549000},"source":"Crossref","is-referenced-by-count":28,"title":["Prostate cancer early diagnosis: circulating microRNA pairs potentially beyond single microRNAs upon 1231 serum samples"],"prefix":"10.1093","volume":"22","author":[{"given":"Hua-Ping","family":"Liu","sequence":"first","affiliation":[{"name":"Bioinformatics at Harbin Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Ming","family":"Lai","sequence":"additional","affiliation":[{"name":"King's College London"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4466-6026","authenticated-orcid":false,"given":"Zheng","family":"Guo","sequence":"additional","affiliation":[{"name":"King's College London"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,7,1]]},"reference":[{"key":"2021052110024193000_ref1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J Clin"},{"key":"2021052110024193000_ref2","volume-title":"SEER Cancer Statistics Review, 1975\u20132016","author":"Howlader"},{"key":"2021052110024193000_ref3","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.eururo.2012.05.068","article-title":"Screening for prostate cancer decreases the risk of developing metastatic disease: findings from the European randomized study of screening for prostate cancer (ERSPC)","volume":"62","author":"Schroder","year":"2012","journal-title":"Eur Urol"},{"key":"2021052110024193000_ref4","doi-asserted-by":"crossref","first-page":"e783","DOI":"10.3399\/bjgp14X682861","article-title":"Digital rectal examination in primary care is important for early detection of prostate cancer: a retrospective cohort analysis study","volume":"64","author":"Walsh","year":"2014","journal-title":"Br J Gen Pract"},{"key":"2021052110024193000_ref5","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1370\/afm.2205","article-title":"Digital rectal examination for prostate cancer screening in primary care: a systematic review and meta-analysis","volume":"16","author":"Naji","year":"2018","journal-title":"Ann Fam Med"},{"key":"2021052110024193000_ref6","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S0022-5347(05)68543-6","article-title":"Prostate specific antigen: a decade of discovery--what we have learned and where we are going","volume":"162","author":"Polascik","year":"1999","journal-title":"J Urol"},{"key":"2021052110024193000_ref7","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s11934-012-0277-6","article-title":"The impact of prostate biopsy on urinary symptoms, erectile function, and anxiety","volume":"13","author":"Glaser","year":"2012","journal-title":"Curr Urol Rep"},{"key":"2021052110024193000_ref8","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1741-7015-12-26","article-title":"Empirical estimates of prostate cancer overdiagnosis by age and prostate-specific antigen","volume":"12","author":"Vickers","year":"2014","journal-title":"BMC Med"},{"key":"2021052110024193000_ref9","doi-asserted-by":"crossref","first-page":"1758835918794630","DOI":"10.1177\/1758835918794630","article-title":"Liquid biopsy of cancer: a multimodal diagnostic tool in clinical oncology","volume":"10","author":"Palmirotta","year":"2018","journal-title":"Ther Adv Med Oncol"},{"key":"2021052110024193000_ref10","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1158\/0008-5472.CAN-10-1229","article-title":"Microfluidic-based multiplex qRT-PCR identifies diagnostic and prognostic microRNA signatures in the sera of prostate cancer patients","volume":"71","author":"Moltzahn","year":"2011","journal-title":"Cancer Res"},{"key":"2021052110024193000_ref11","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1002\/pros.22495","article-title":"A panel of five circulating microRNAs as potential biomarkers for prostate cancer","volume":"72","author":"Chen","year":"2012","journal-title":"Prostate"},{"key":"2021052110024193000_ref12","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s13346-013-0169-4","article-title":"Profiling of circulating microRNAs for prostate cancer biomarker discovery","volume":"4","author":"Haldrup","year":"2014","journal-title":"Drug Deliv Transl Res"},{"key":"2021052110024193000_ref13","doi-asserted-by":"crossref","first-page":"4867","DOI":"10.1007\/s13277-014-1638-1","article-title":"Circulatory miR-628-5p is downregulated in prostate cancer patients","volume":"35","author":"Srivastava","year":"2014","journal-title":"Tumour Biol"},{"key":"2021052110024193000_ref14","doi-asserted-by":"crossref","first-page":"900","DOI":"10.3389\/fonc.2019.00900","article-title":"Circulating MicroRNAs as biomarkers for prostate cancer detection and metastasis development prediction","volume":"9","author":"Bidarra","year":"2019","journal-title":"Front Oncol"},{"key":"2021052110024193000_ref15","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1093\/carcin\/bgy167","article-title":"Circulating microRNAs combined with PSA for accurate and non-invasive prostate cancer detection","volume":"40","author":"Mello-Grand","year":"2019","journal-title":"Carcinogenesis"},{"key":"2021052110024193000_ref16","doi-asserted-by":"crossref","first-page":"3016","DOI":"10.1158\/1078-0432.CCR-18-2849","article-title":"Large-scale circulating microRNA profiling for the liquid biopsy of prostate cancer","volume":"25","author":"Urabe","year":"2019","journal-title":"Clin Cancer Res"},{"key":"2021052110024193000_ref17","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1002\/pros.23485","article-title":"Circulating microRNAs in plasma as potential biomarkers for the early detection of prostate cancer","volume":"78","author":"McDonald","year":"2018","journal-title":"Prostate"},{"key":"2021052110024193000_ref18","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.eururo.2014.07.035","article-title":"Exosomal miR-1290 and miR-375 as prognostic markers in castration-resistant prostate cancer","volume":"67","author":"Huang","year":"2015","journal-title":"Eur Urol"},{"key":"2021052110024193000_ref19","first-page":"1570","article-title":"miR-1290 is a potential prognostic biomarker in non-small cell lung cancer","volume":"7","author":"Mo","year":"2015","journal-title":"J Thorac Dis"},{"key":"2021052110024193000_ref20","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1093\/annonc\/mdw279","article-title":"Circulating microRNA-1290 as a novel diagnostic and prognostic biomarker in human colorectal cancer","volume":"27","author":"Imaoka","year":"2016","journal-title":"Ann Oncol"},{"key":"2021052110024193000_ref21","doi-asserted-by":"crossref","first-page":"3600","DOI":"10.1158\/1078-0432.CCR-12-3092","article-title":"MicroRNA array analysis finds elevated serum miR-1290 accurately distinguishes patients with low-stage pancreatic cancer from healthy and disease controls","volume":"19","author":"Li","year":"2013","journal-title":"Clin Cancer Res"},{"key":"2021052110024193000_ref22","doi-asserted-by":"crossref","first-page":"189","DOI":"10.3892\/mco.2016.875","article-title":"Profiling analysis of circulating microRNA expression in cervical cancer","volume":"5","author":"Nagamitsu","year":"2016","journal-title":"Mol Clin Oncol"},{"key":"2021052110024193000_ref23","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s13048-018-0458-0","article-title":"Exosomal miR-1290 is a potential biomarker of high-grade serous ovarian carcinoma and can discriminate patients from those with malignancies of other histological types","volume":"11","author":"Kobayashi","year":"2018","journal-title":"J Ovarian Res"},{"key":"2021052110024193000_ref24","doi-asserted-by":"crossref","first-page":"1010428319826853","DOI":"10.1177\/1010428319826853","article-title":"Circulating miRNA-1290 as a potential biomarker for response to chemoradiotherapy and prognosis of patients with advanced oral squamous cell carcinoma: a single-center retrospective study","volume":"41","author":"Nakashima","year":"2019","journal-title":"Tumour Biol"},{"key":"2021052110024193000_ref25","doi-asserted-by":"crossref","first-page":"920","DOI":"10.7150\/thno.30339","article-title":"Serum miR-626 and miR-5100 are promising prognosis predictors for oral squamous cell carcinoma","volume":"9","author":"Shi","year":"2019","journal-title":"Theranostics"},{"key":"2021052110024193000_ref26","first-page":"3592","article-title":"Increasing expression of miR-5100 in non-small-cell lung cancer and correlation with prognosis","volume":"21","author":"Wang","year":"2017","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"2021052110024193000_ref27","doi-asserted-by":"crossref","first-page":"20","DOI":"10.4161\/auto.22397","article-title":"Autophagy is differentially induced in prostate cancer LNCaP, DU145 and PC-3 cells via distinct splicing profiles of ATG5","volume":"9","author":"Ouyang","year":"2013","journal-title":"Autophagy"},{"key":"2021052110024193000_ref28","doi-asserted-by":"crossref","first-page":"121826","DOI":"10.1155\/2015\/121826","article-title":"Roles of autophagy induced by natural compounds in prostate cancer","volume":"2015","author":"Naponelli","year":"2015","journal-title":"Biomed Res Int"},{"key":"2021052110024193000_ref29","doi-asserted-by":"crossref","DOI":"10.3390\/biom9040131","article-title":"Splicing factors have an essential role in prostate cancer progression and androgen receptor signaling","volume":"9","author":"Takayama","year":"2019","journal-title":"Biomolecules"},{"key":"2021052110024193000_ref30","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1038\/s41571-018-0085-0","article-title":"Alternative splicing in prostate cancer","volume":"15","author":"Paschalis","year":"2018","journal-title":"Nat Rev Clin Oncol"},{"key":"2021052110024193000_ref31","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1677\/ERC-08-0043","article-title":"Endocrine disruptors and prostate cancer risk","volume":"15","author":"Prins","year":"2008","journal-title":"Endocr Relat Cancer"},{"key":"2021052110024193000_ref32","doi-asserted-by":"crossref","first-page":"2414","DOI":"10.1002\/ijc.31165","article-title":"The dark side of glucose transporters in prostate cancer: are they a new feature to characterize carcinomas?","volume":"142","author":"Gonzalez-Menendez","year":"2018","journal-title":"Int J Cancer"},{"key":"2021052110024193000_ref33","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1007\/s40572-017-0137-0","article-title":"Polluted pathways: mechanisms of metabolic disruption by endocrine disrupting chemicals","volume":"4","author":"Mimoto","year":"2017","journal-title":"Curr Environ Health Rep"},{"key":"2021052110024193000_ref34","doi-asserted-by":"crossref","first-page":"D239","DOI":"10.1093\/nar\/gkx1141","article-title":"DIANA-TarBase v8: a decade-long collection of experimentally supported miRNA-gene interactions","volume":"46","author":"Karagkouni","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"2021052110024193000_ref35","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets","volume":"10","author":"Zhou","year":"2019","journal-title":"Nat Commun"}],"container-title":["Briefings in Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/bib\/article-pdf\/22\/3\/bbaa111\/37963156\/bbaa111.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/bib\/article-pdf\/22\/3\/bbaa111\/37963156\/bbaa111.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T10:03:19Z","timestamp":1621591399000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bib\/article\/doi\/10.1093\/bib\/bbaa111\/5865576"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,1]]},"references-count":35,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,5,20]]}},"URL":"https:\/\/doi.org\/10.1093\/bib\/bbaa111","relation":{},"ISSN":["1467-5463","1477-4054"],"issn-type":[{"value":"1467-5463","type":"print"},{"value":"1477-4054","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,5]]},"published":{"date-parts":[[2020,7,1]]},"article-number":"bbaa111"}}