{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T13:16:58Z","timestamp":1768742218033,"version":"3.49.0"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T00:00:00Z","timestamp":1739491200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82201522"],"award-info":[{"award-number":["82201522"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Plan on enhancing scientific research in GMU"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Prostate-specific antigen (PSA) is commonly used as a biomarker to diagnose and predict the course of prostate cancer (PCa). However, PSA detection is susceptible to changes in the physiologic environment, which may lead to some misdiagnosis. Thus, it is crucial to find a novel diagnostic marker.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We accessed microRNA (miRNA) expression datasets (GSE206793 and GSE112264) from the GEO database, analyzing peripheral blood samples from PCa patients. Differentially expressed miRNAs (DEmiRNAs) were identified using GEO2R. A specific miRNA, miR-455-3p, was pinpointed through rigorous analysis of clinical correlations and ROC curves. Peripheral blood samples from healthy individuals and PCa patients were subjected to qRT-PCR validation, aligning results with the GSE206793 dataset. The miRWalk database was utilized to predict downstream genes, while STRING facilitated the construction of a protein-protein interaction (PPI) network. KEGG pathway analysis enriched our understanding of potential molecular pathways.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>We found that miR-455-3p was highly expressed in the peripheral blood of PCa patients with Gleason score (GS) \u2265 8, while independent of T stage, age and PSA. ROC analysis revealed a favorable diagnostic efficacy of miR-455-3p and AUC for the two datasets was respectively 0.943 and 0.847. The qRT-PCR assay also revealed consistent results. Interestingly, the PSA levels of P1 (GS = 5 + 4) and P6 (GS = 3 + 3) were respectively 3.38 and 4.45 ng\/ml, while miR-455-3p was highly expressed in both, suggesting its low misdiagnosis. The speculation was validated in GSE206793 dataset. Finally, 9 potential targets of miR-455-3p were predicted. PPI network revealed PPP2R2A, ITGB1 and CDKN1A as key nodes. KEGG pathway analysis revealed that they were enriched in various cancers, biological processes and molecular signals.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Our study identifies miR-455-3p as a promising diagnostic marker for PCa, outperforming PSA in terms of specificity and sensitivity. The robustness of miR-455-3p, coupled with its potential downstream targets and associated pathways, highlights its clinical significance for improved PCa diagnosis and management.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0317385","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T18:24:55Z","timestamp":1739557495000},"page":"e0317385","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["miR-455-3p has superior diagnostic potential to PSA in peripheral blood for prostate cancer"],"prefix":"10.1371","volume":"20","author":[{"given":"Yi","family":"Cen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shourui","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuyu","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Churuo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangjin","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuan","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zeyu","family":"Zha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiyan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6798-2107","authenticated-orcid":true,"given":"Guangbin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,2,14]]},"reference":[{"issue":"6","key":"pone.0317385.ref001","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1097\/JU.0000000000003452","article-title":"Updates to Advanced Prostate Cancer: AUA\/SUO Guideline (2023).","volume":"209","author":"W Lowrance","year":"2023","journal-title":"J Urol"},{"issue":"9","key":"pone.0317385.ref002","doi-asserted-by":"crossref","DOI":"10.1530\/ERC-22-0360","article-title":"Prostate cancer and bone: clinical presentation and molecular mechanisms","volume":"30","author":"KV Wells","year":"2023","journal-title":"Endocr Relat Cancer"},{"issue":"24","key":"pone.0317385.ref003","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1001\/jama.2017.7248","article-title":"The Diagnosis and Treatment of Prostate Cancer: A Review","volume":"317","author":"MS Litwin","year":"2017","journal-title":"JAMA"},{"issue":"3","key":"pone.0317385.ref004","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.eururo.2008.11.040","article-title":"Screening for prostate cancer in 2008 II: the importance of molecular subforms of prostate-specific antigen and tissue kallikreins.","volume":"55","author":"FH Jansen","year":"2009","journal-title":"Eur Urol."},{"issue":"5","key":"pone.0317385.ref005","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.urolonc.2008.03.007","article-title":"Local-regional prostate cancer","volume":"26","author":"MJ Jones","year":"2008","journal-title":"Urol Oncol"},{"issue":"3","key":"pone.0317385.ref006","doi-asserted-by":"crossref","first-page":"746","DOI":"10.7150\/thno.23906","article-title":"Erratum: Improvement of Prostate Cancer Diagnosis by Detecting PSA Glycosylation-Specific Changes: Erratum.","volume":"8","author":"E Llop","year":"2018","journal-title":"Theranostics"},{"issue":"24","key":"pone.0317385.ref007","article-title":"Deciphering miRNAs\u2019 Action through miRNA Editing.","volume":"20","author":"DSM Correia","year":"2019","journal-title":"Int J Mol Sci."},{"issue":"2","key":"pone.0317385.ref008","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.cell.2009.01.002","article-title":"MicroRNAs: target recognition and regulatory functions","volume":"136","author":"DP Bartel","year":"2009","journal-title":"Cell"},{"issue":"1","key":"pone.0317385.ref009","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1080\/07853890.2022.2071459","article-title":"The role of miRNA-210 in pre-eclampsia development","volume":"54","author":"I Jaszczuk","year":"2022","journal-title":"Ann Med"},{"issue":"24","key":"pone.0317385.ref010","doi-asserted-by":"crossref","first-page":"2635","DOI":"10.1080\/15384101.2022.2108128","article-title":"Upregulated miR-322-5p regulates cell cycle and promotes cell proliferation and apoptosis by directly targeting Wee1 in mice liver injury","volume":"21","author":"H Tong","year":"2022","journal-title":"Cell Cycle"},{"issue":"19","key":"pone.0317385.ref011","doi-asserted-by":"crossref","DOI":"10.3390\/ijms231911502","article-title":"miRNA: A Promising Therapeutic Target in Cancer.","volume":"23","author":"A Menon","year":"2022","journal-title":"Int J Mol Sci"},{"key":"pone.0317385.ref012","first-page":"577","article-title":"Circulating microRNA-122a as a diagnostic marker for hepatocellular carcinoma.","volume":"6","author":"J Luo","year":"2013","journal-title":"Onco Targets Ther"},{"key":"pone.0317385.ref013","doi-asserted-by":"crossref","first-page":"100825","DOI":"10.1016\/j.mam.2019.10.002","article-title":"Circulating miRNA analysis for cancer diagnostics and therapy","volume":"72","author":"L Valihrach","year":"2020","journal-title":"Mol Aspects Med"},{"issue":"2","key":"pone.0317385.ref014","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/jso.23358","article-title":"MiRNA-199a-3p: A potential circulating diagnostic biomarker for early gastric cancer","volume":"108","author":"C Li","year":"2013","journal-title":"J Surg Oncol"},{"key":"pone.0317385.ref015","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/978-1-4939-3578-9_5","article-title":"The Gene Expression Omnibus Database.","volume":"1418","author":"E Clough","year":"2016","journal-title":"Methods Mol Biol"},{"issue":"6","key":"pone.0317385.ref016","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative C(T) method.","volume":"3","author":"TD Schmittgen","year":"2008","journal-title":"Nat Protoc."},{"key":"pone.0317385.ref017","doi-asserted-by":"crossref","first-page":"210686","DOI":"10.1155\/2013\/210686","article-title":"Bone-targeted therapies in metastatic castration-resistant prostate cancer: evolving paradigms","volume":"2013","author":"J El-Amm","year":"2013","journal-title":"Prostate Cancer"},{"issue":"4","key":"pone.0317385.ref018","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nrurol.2014.42","article-title":"Prostate cancer in Asian men","volume":"11","author":"K. Ito","year":"2014","journal-title":"Nat Rev Urol"},{"issue":"1","key":"pone.0317385.ref019","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21551","article-title":"Cancer statistics, 2019.","volume":"69","author":"RL Siegel","year":"2019","journal-title":"CA Cancer J Clin."},{"key":"pone.0317385.ref020","doi-asserted-by":"crossref","first-page":"146170","DOI":"10.1155\/2014\/146170","article-title":"MicroRNA as new tools for prostate cancer risk assessment and therapeutic intervention: results from clinical data set and patients\u2019 samples","volume":"2014","author":"A Cannistraci","year":"2014","journal-title":"Biomed Res Int"},{"issue":"5","key":"pone.0317385.ref021","first-page":"6643","article-title":"Serum levels of candidate microRNA diagnostic markers differ among the stages of non-small-cell lung cancer","volume":"16","author":"T Aiso","year":"2018","journal-title":"Oncol Lett"},{"key":"pone.0317385.ref022","doi-asserted-by":"crossref","first-page":"1073328","DOI":"10.3389\/fendo.2022.1073328","article-title":"Heterogeneous circulating miRNA profiles of PBMAH.","volume":"13","author":"K Hara","year":"2022","journal-title":"Front Endocrinol (Lausanne)."},{"issue":"3","key":"pone.0317385.ref023","article-title":"Circulating MicroRNA Biomarkers for Lung Cancer Detection in East Asian Populations.","volume":"11","author":"H Yu","year":"2019","journal-title":"Cancers (Basel)."},{"key":"pone.0317385.ref024","doi-asserted-by":"crossref","first-page":"15980","DOI":"10.1038\/srep15980","article-title":"Heterogeneity of miR-10b expression in circulating tumor cells.","volume":"5","author":"C Gasch","year":"2015","journal-title":"Sci Rep."},{"issue":"6","key":"pone.0317385.ref025","first-page":"6150","article-title":"Identification of differentially expressed microRNAs and the potential of microRNA-455-3p as a novel prognostic biomarker in glioma.","volume":"18","author":"W Wang","year":"2019","journal-title":"Oncol Lett."},{"issue":"1","key":"pone.0317385.ref026","doi-asserted-by":"crossref","first-page":"23756","DOI":"10.1038\/s41598-021-03222-x","article-title":"Detection of increased serum miR-122-5p and miR-455-3p levels before the clinical diagnosis of liver cancer in people with type 2 diabetes.","volume":"11","author":"HM Lee","year":"2021","journal-title":"Sci Rep."},{"issue":"10","key":"pone.0317385.ref027","doi-asserted-by":"crossref","first-page":"2621","DOI":"10.1007\/s00277-021-04573-1","article-title":"Circulating miR-455-3p, miR-5787, and miR-548a-3p as potential noninvasive biomarkers in the diagnosis of acute graft-versus-host disease: a validation study","volume":"100","author":"J Motaei","year":"2021","journal-title":"Ann Hematol"},{"issue":"1","key":"pone.0317385.ref028","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23010554","article-title":"The microRNA-455 Null Mouse Has Memory Deficit and Increased Anxiety, Targeting Key Genes Involved in Alzheimer\u2019s Disease.","volume":"23","author":"TE Swingler","year":"2022","journal-title":"Int J Mol Sci."},{"key":"pone.0317385.ref029","doi-asserted-by":"crossref","first-page":"669590","DOI":"10.3389\/fphys.2021.669590","article-title":"A Four-MicroRNA Panel in Peripheral Blood Identified as an Early Biomarker to Diagnose Acute Myocardial Infarction.","volume":"12","author":"L Chen","year":"2021","journal-title":"Front Physiol"},{"issue":"3","key":"pone.0317385.ref030","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/ijc.11711","article-title":"Cumulative probability of PSA increase above 4.0 NG\/ML in population-based screening for prostate cancer","volume":"109","author":"K Ito","year":"2004","journal-title":"Int J Cancer"},{"issue":"8","key":"pone.0317385.ref031","doi-asserted-by":"crossref","first-page":"249","DOI":"10.4329\/wjr.v14.i8.249","article-title":"Augmenting prostate magnetic resonance imaging reporting to incorporate diagnostic recommendations based upon clinical risk calculators","volume":"14","author":"K Gupta","year":"2022","journal-title":"World J Radiol"},{"key":"pone.0317385.ref032","first-page":"8730608","article-title":"Detection and Prognosis of Prostate Cancer Using Blood-Based Biomarkers.","volume":"2020","author":"W Jin","year":"2020","journal-title":"Mediators Inflamm"},{"issue":"4","key":"pone.0317385.ref033","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1159\/000020161","article-title":"Inflammation in prostate biopsies of men without prostatic malignancy or clinical prostatitis: correlation with total serum PSA and PSA density","volume":"37","author":"PH Schatteman","year":"2000","journal-title":"Eur Urol"},{"key":"pone.0317385.ref034","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.biopha.2015.07.015","article-title":"Upregulation of miR-556-5p promoted prostate cancer cell proliferation by suppressing PPP2R2A expression.","volume":"75","author":"W Zhao","year":"2015","journal-title":"Biomed Pharmacother."},{"issue":"3","key":"pone.0317385.ref035","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1111\/jcmm.12760","article-title":"miR-222 attenuates cisplatin-induced cell death by targeting the PPP2R2A\/Akt\/mTOR Axis in bladder cancer cells","volume":"20","author":"LP Zeng","year":"2016","journal-title":"J Cell Mol Med"},{"issue":"1","key":"pone.0317385.ref036","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1111\/cas.12842","article-title":"Tumor-suppressive microRNA-223 inhibits cancer cell migration and invasion by targeting ITGA3\/ITGB1 signaling in prostate cancer","volume":"107","author":"A Kurozumi","year":"2016","journal-title":"Cancer Sci"},{"issue":"6","key":"pone.0317385.ref037","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41419-021-03870-x","article-title":"HJURP promotes proliferation in prostate cancer cells through increasing CDKN1A degradation via the GSK3beta\/JNK signaling pathway.","volume":"12","author":"W Lai","year":"2021","journal-title":"Cell Death Dis."},{"issue":"1","key":"pone.0317385.ref038","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.1038\/s41598-018-20161-2","article-title":"ITGB1-dependent upregulation of Caveolin-1 switches TGFbeta signalling from tumour-suppressive to oncogenic in prostate cancer","volume":"8","author":"T Pellinen","year":"2018","journal-title":"Sci Rep"},{"issue":"10","key":"pone.0317385.ref039","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.4161\/cc.24741","article-title":"Deletion of p21\/Cdkn1a confers protective effect against prostate tumorigenesis in transgenic adenocarcinoma of the mouse prostate model","volume":"12","author":"AK Jain","year":"2013","journal-title":"Cell Cycle"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0317385","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T18:25:22Z","timestamp":1739557522000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0317385"}},"subtitle":[],"editor":[{"given":"Gurudeeban","family":"Selvaraj","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,2,14]]},"references-count":39,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2,14]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0317385","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,14]]}}}