Comprehensive microRNA analysis identifies miR-24 and miR-125a-5p as plasma biomarkers for rheumatoid arthritis
MicroRNAs (miRNAs) are present in human plasma and known as a non-invasive biomarker for cancer detection. Our study was designed to identify plasma miRNAs specific for rheumatoid arthritis (RA) by a comprehensive array approach. We performed a systematic, array-based miRNA analysis on plasma sample...
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| Veröffentlicht in: | PloS one 2013-07, Vol.8 (7), p.e69118 |
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| creator | Murata, Koichi Furu, Moritoshi Yoshitomi, Hiroyuki Ishikawa, Masahiro Shibuya, Hideyuki Hashimoto, Motomu Imura, Yoshitaka Fujii, Takao Ito, Hiromu Mimori, Tsuneyo Matsuda, Shuichi |
| description | MicroRNAs (miRNAs) are present in human plasma and known as a non-invasive biomarker for cancer detection. Our study was designed to identify plasma miRNAs specific for rheumatoid arthritis (RA) by a comprehensive array approach. We performed a systematic, array-based miRNA analysis on plasma samples from three RA patients and three healthy controls (HCs). Plasma miRNAs with more than four times change or with significant (P |
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Our study was designed to identify plasma miRNAs specific for rheumatoid arthritis (RA) by a comprehensive array approach. We performed a systematic, array-based miRNA analysis on plasma samples from three RA patients and three healthy controls (HCs). Plasma miRNAs with more than four times change or with significant (P<0.05) change in expression, or detectable only in RA plasma, were confirmed with plasma from eight RA patients and eight HCs using real-time quantitative PCR. Consistently detectable miRNAs that were significantly different between RA patients and HCs were chosen for further validation with 102 RA patients and 104 HCs. The area under curves (AUC) were calculated after plotting the receiver operating characteristic (ROC) curves. To determine if these miRNAs are specific for RA, the concentrations of these miRNAs were analyzed in 24 patients with osteoarthritis (OA), and 11 patients with systemic lupus erythematosus (SLE). The array analysis and the subsequent confirmation in larger patient cohort identified significant alterations in plasma levels of seven miRNAs. The highest AUC was found for miR-125a-5p, followed in order by miR-24 and miR-26a. Multivariable logistic regression analysis showed that miR-24, miR-30a-5p, and miR-125a-5p were crucial factors for making detection model of RA and provided a formula for Estimated Probability of RA by plasma MiRNA (ePRAM), employing miR-24, miR-30a-5p and miR-125a-5p, which showed increased diagnostic accuracy (AUC: 0.89). The level of miR-24, miR-125a-5p, and ePRAM in OA and SLE patients were lower than that in RA. There was no significant difference in detection for anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA patients. These results suggest that the plasma concentrations of miR-24 and miR-125a-5p, and ePRAM are potential diagnostic markers of RA even if patients were ACPA-negative.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0069118</identifier><identifier>PMID: 23874885</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Area Under Curve ; Arthritis ; Arthritis, Rheumatoid - blood ; Autoimmune diseases ; Biocompatibility ; Biology ; Biomarkers ; Biomarkers - blood ; Biomedical materials ; Blood plasma ; Breast cancer ; Cancer ; Cancer therapies ; Change detection ; Chronic conditions ; Citrulline ; Diagnostic systems ; Disease ; Humans ; Immunology ; Logistic Models ; Lupus ; Mathematics ; Medical diagnosis ; Medicine ; MicroRNA ; MicroRNAs ; MicroRNAs - blood ; miRNA ; Osteoarthritis ; Patients ; Plasma levels ; Real-Time Polymerase Chain Reaction ; Regression analysis ; Rheumatic diseases ; Rheumatoid arthritis ; Rheumatoid factor ; Rheumatology ; Ribonucleic acid ; RNA ; ROC Curve ; Somatotropin ; Statistical analysis ; Surgery ; Systemic lupus erythematosus ; University graduates</subject><ispartof>PloS one, 2013-07, Vol.8 (7), p.e69118</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Murata et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Murata et al 2013 Murata et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c802t-dab522271b0fbeceaef915c0c01b5983232092b644794aa6e7d057f460af020f3</citedby><cites>FETCH-LOGICAL-c802t-dab522271b0fbeceaef915c0c01b5983232092b644794aa6e7d057f460af020f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715465/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715465/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23874885$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Jin, Dong-Yan</contributor><creatorcontrib>Murata, Koichi</creatorcontrib><creatorcontrib>Furu, Moritoshi</creatorcontrib><creatorcontrib>Yoshitomi, Hiroyuki</creatorcontrib><creatorcontrib>Ishikawa, Masahiro</creatorcontrib><creatorcontrib>Shibuya, Hideyuki</creatorcontrib><creatorcontrib>Hashimoto, Motomu</creatorcontrib><creatorcontrib>Imura, Yoshitaka</creatorcontrib><creatorcontrib>Fujii, Takao</creatorcontrib><creatorcontrib>Ito, Hiromu</creatorcontrib><creatorcontrib>Mimori, Tsuneyo</creatorcontrib><creatorcontrib>Matsuda, Shuichi</creatorcontrib><title>Comprehensive microRNA analysis identifies miR-24 and miR-125a-5p as plasma biomarkers for rheumatoid arthritis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>MicroRNAs (miRNAs) are present in human plasma and known as a non-invasive biomarker for cancer detection. Our study was designed to identify plasma miRNAs specific for rheumatoid arthritis (RA) by a comprehensive array approach. We performed a systematic, array-based miRNA analysis on plasma samples from three RA patients and three healthy controls (HCs). Plasma miRNAs with more than four times change or with significant (P<0.05) change in expression, or detectable only in RA plasma, were confirmed with plasma from eight RA patients and eight HCs using real-time quantitative PCR. Consistently detectable miRNAs that were significantly different between RA patients and HCs were chosen for further validation with 102 RA patients and 104 HCs. The area under curves (AUC) were calculated after plotting the receiver operating characteristic (ROC) curves. To determine if these miRNAs are specific for RA, the concentrations of these miRNAs were analyzed in 24 patients with osteoarthritis (OA), and 11 patients with systemic lupus erythematosus (SLE). The array analysis and the subsequent confirmation in larger patient cohort identified significant alterations in plasma levels of seven miRNAs. The highest AUC was found for miR-125a-5p, followed in order by miR-24 and miR-26a. Multivariable logistic regression analysis showed that miR-24, miR-30a-5p, and miR-125a-5p were crucial factors for making detection model of RA and provided a formula for Estimated Probability of RA by plasma MiRNA (ePRAM), employing miR-24, miR-30a-5p and miR-125a-5p, which showed increased diagnostic accuracy (AUC: 0.89). The level of miR-24, miR-125a-5p, and ePRAM in OA and SLE patients were lower than that in RA. There was no significant difference in detection for anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA patients. These results suggest that the plasma concentrations of miR-24 and miR-125a-5p, and ePRAM are potential diagnostic markers of RA even if patients were ACPA-negative.</description><subject>Analysis</subject><subject>Area Under Curve</subject><subject>Arthritis</subject><subject>Arthritis, Rheumatoid - blood</subject><subject>Autoimmune diseases</subject><subject>Biocompatibility</subject><subject>Biology</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>Biomedical materials</subject><subject>Blood plasma</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Change detection</subject><subject>Chronic conditions</subject><subject>Citrulline</subject><subject>Diagnostic systems</subject><subject>Disease</subject><subject>Humans</subject><subject>Immunology</subject><subject>Logistic Models</subject><subject>Lupus</subject><subject>Mathematics</subject><subject>Medical diagnosis</subject><subject>Medicine</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - blood</subject><subject>miRNA</subject><subject>Osteoarthritis</subject><subject>Patients</subject><subject>Plasma levels</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Regression analysis</subject><subject>Rheumatic diseases</subject><subject>Rheumatoid arthritis</subject><subject>Rheumatoid factor</subject><subject>Rheumatology</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>ROC Curve</subject><subject>Somatotropin</subject><subject>Statistical analysis</subject><subject>Surgery</subject><subject>Systemic lupus erythematosus</subject><subject>University graduates</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkltr3DAQhU1padK0_6C0hkKhD95KsizZL4Vl6WUhNLC9vIqxPVortS1HskPz76tknbCGFoofLDTfHA1nThS9pGRFU0nfX9rJ9dCuBtvjihBRUJo_ik5pkbJEMJI-PjqfRM-8vyQkS3MhnkYnLM0lz_PsNLIb2w0OG-y9uca4M5Wzu6_rGIL0jTc-NjX2o9EGfSjuEsZDqb47UpZBkg0x-HhowXcQl8Z24H6h87G2LnYNTh2M1tQxuLFxZjT-efREQ-vxxfw_i358-vh98yU5v_i83azPkyonbExqKDPGmKQl0SVWCKgLmlWkIrTMijxlKSMFKwXnsuAAAmVNMqm5IKAJIzo9i14fdIfWejV75RXlTKaSsFwEYnsgaguXanAmjH6jLBh1d2HdXoWpTdWi4jnUJRVCYFFy5AWUWkodLCxAV0xi0PowvzaVHdZVsMxBuxBdVnrTqL29VmGRGRdZEHgzCzh7NaEf_zHyTO0hTGV6bYNY1RlfqTWXOWNhvzJQq79Q4asxrDekRZtwv2h4t2gIzIi_xz1M3qvtt93_sxc_l-zbI7ZBaMfG23Yaje39EuQHMITPe4f6wTlK1G3Y791Qt2FXc9hD26tj1x-a7tOd_gGZBPoc</recordid><startdate>20130718</startdate><enddate>20130718</enddate><creator>Murata, Koichi</creator><creator>Furu, Moritoshi</creator><creator>Yoshitomi, Hiroyuki</creator><creator>Ishikawa, Masahiro</creator><creator>Shibuya, Hideyuki</creator><creator>Hashimoto, Motomu</creator><creator>Imura, Yoshitaka</creator><creator>Fujii, Takao</creator><creator>Ito, Hiromu</creator><creator>Mimori, Tsuneyo</creator><creator>Matsuda, Shuichi</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130718</creationdate><title>Comprehensive microRNA analysis identifies miR-24 and miR-125a-5p as plasma biomarkers for rheumatoid arthritis</title><author>Murata, Koichi ; Furu, Moritoshi ; Yoshitomi, Hiroyuki ; Ishikawa, Masahiro ; Shibuya, Hideyuki ; Hashimoto, Motomu ; Imura, Yoshitaka ; Fujii, Takao ; Ito, Hiromu ; Mimori, Tsuneyo ; Matsuda, Shuichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c802t-dab522271b0fbeceaef915c0c01b5983232092b644794aa6e7d057f460af020f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Analysis</topic><topic>Area Under Curve</topic><topic>Arthritis</topic><topic>Arthritis, Rheumatoid - blood</topic><topic>Autoimmune diseases</topic><topic>Biocompatibility</topic><topic>Biology</topic><topic>Biomarkers</topic><topic>Biomarkers - blood</topic><topic>Biomedical materials</topic><topic>Blood plasma</topic><topic>Breast cancer</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Change detection</topic><topic>Chronic conditions</topic><topic>Citrulline</topic><topic>Diagnostic systems</topic><topic>Disease</topic><topic>Humans</topic><topic>Immunology</topic><topic>Logistic Models</topic><topic>Lupus</topic><topic>Mathematics</topic><topic>Medical diagnosis</topic><topic>Medicine</topic><topic>MicroRNA</topic><topic>MicroRNAs</topic><topic>MicroRNAs - blood</topic><topic>miRNA</topic><topic>Osteoarthritis</topic><topic>Patients</topic><topic>Plasma levels</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Regression analysis</topic><topic>Rheumatic diseases</topic><topic>Rheumatoid arthritis</topic><topic>Rheumatoid factor</topic><topic>Rheumatology</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>ROC Curve</topic><topic>Somatotropin</topic><topic>Statistical analysis</topic><topic>Surgery</topic><topic>Systemic lupus erythematosus</topic><topic>University graduates</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Murata, Koichi</creatorcontrib><creatorcontrib>Furu, Moritoshi</creatorcontrib><creatorcontrib>Yoshitomi, Hiroyuki</creatorcontrib><creatorcontrib>Ishikawa, Masahiro</creatorcontrib><creatorcontrib>Shibuya, Hideyuki</creatorcontrib><creatorcontrib>Hashimoto, Motomu</creatorcontrib><creatorcontrib>Imura, Yoshitaka</creatorcontrib><creatorcontrib>Fujii, Takao</creatorcontrib><creatorcontrib>Ito, Hiromu</creatorcontrib><creatorcontrib>Mimori, Tsuneyo</creatorcontrib><creatorcontrib>Matsuda, Shuichi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Science (Gale in Context)</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>ProQuest Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Database (1962 - 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Our study was designed to identify plasma miRNAs specific for rheumatoid arthritis (RA) by a comprehensive array approach. We performed a systematic, array-based miRNA analysis on plasma samples from three RA patients and three healthy controls (HCs). Plasma miRNAs with more than four times change or with significant (P<0.05) change in expression, or detectable only in RA plasma, were confirmed with plasma from eight RA patients and eight HCs using real-time quantitative PCR. Consistently detectable miRNAs that were significantly different between RA patients and HCs were chosen for further validation with 102 RA patients and 104 HCs. The area under curves (AUC) were calculated after plotting the receiver operating characteristic (ROC) curves. To determine if these miRNAs are specific for RA, the concentrations of these miRNAs were analyzed in 24 patients with osteoarthritis (OA), and 11 patients with systemic lupus erythematosus (SLE). The array analysis and the subsequent confirmation in larger patient cohort identified significant alterations in plasma levels of seven miRNAs. The highest AUC was found for miR-125a-5p, followed in order by miR-24 and miR-26a. Multivariable logistic regression analysis showed that miR-24, miR-30a-5p, and miR-125a-5p were crucial factors for making detection model of RA and provided a formula for Estimated Probability of RA by plasma MiRNA (ePRAM), employing miR-24, miR-30a-5p and miR-125a-5p, which showed increased diagnostic accuracy (AUC: 0.89). The level of miR-24, miR-125a-5p, and ePRAM in OA and SLE patients were lower than that in RA. There was no significant difference in detection for anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA patients. These results suggest that the plasma concentrations of miR-24 and miR-125a-5p, and ePRAM are potential diagnostic markers of RA even if patients were ACPA-negative.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23874885</pmid><doi>10.1371/journal.pone.0069118</doi><tpages>e69118</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Analysis Area Under Curve Arthritis Arthritis, Rheumatoid - blood Autoimmune diseases Biocompatibility Biology Biomarkers Biomarkers - blood Biomedical materials Blood plasma Breast cancer Cancer Cancer therapies Change detection Chronic conditions Citrulline Diagnostic systems Disease Humans Immunology Logistic Models Lupus Mathematics Medical diagnosis Medicine MicroRNA MicroRNAs MicroRNAs - blood miRNA Osteoarthritis Patients Plasma levels Real-Time Polymerase Chain Reaction Regression analysis Rheumatic diseases Rheumatoid arthritis Rheumatoid factor Rheumatology Ribonucleic acid RNA ROC Curve Somatotropin Statistical analysis Surgery Systemic lupus erythematosus University graduates |
| title | Comprehensive microRNA analysis identifies miR-24 and miR-125a-5p as plasma biomarkers for rheumatoid arthritis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-24T22%3A18%3A58IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Comprehensive%20microRNA%20analysis%20identifies%20miR-24%20and%20miR-125a-5p%20as%20plasma%20biomarkers%20for%20rheumatoid%20arthritis&rft.jtitle=PloS%20one&rft.au=Murata,%20Koichi&rft.date=2013-07-18&rft.volume=8&rft.issue=7&rft.spage=e69118&rft.pages=e69118-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0069118&rft_dat=%3Cgale_plos_%3EA478225387%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1427370286&rft_id=info:pmid/23874885&rft_galeid=A478225387&rft_doaj_id=oai_doaj_org_article_48adb1666e9b4e49abf77f8749afc27e&rfr_iscdi=true |