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Currently, there is no clinically viable non-invasive biomarker assay for early detection, thus limiting the effective prevention and therapeutic strategies for PE.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We conducted a discovery\u2013training\u2013validation three-phase retrospective and prospective study with cross-platform and multicenter cohorts. The initial biomarkers were discovered and verified in tissue specimens by small RNA sequencing and qRT-PCR. A miRNA signature (miR2PE-score) was developed using Firth\u2019s bias-reduced logistic regression analysis and subsequently validated in two independent multinational retrospective cohorts and two prospective plasma cohorts.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We initially identified five PE-associated differentially expressed miRNAs from miRNA sequencing data and subsequently validated two miRNAs (<jats:italic>miR-196b-5p<\/jats:italic> and <jats:italic>miR-584-5p<\/jats:italic>) as robust biomarkers by association analysis with clinical characteristics and qRT-PCR in tissue specimens in the discovery phase. Using Firth\u2019s bias-reduced logistic regression analysis, we developed the miR2PE-score for the early detection of PE. The miR2PE-score showed a high diagnostic performance with an area under the receiver operating characteristic curve (AUROC) of 0.920, 0.848, 0.864, and 0.812 in training, internal, and two external validation cross-platform and multicenter cohorts, respectively. Finally, we demonstrated the non-invasive diagnostic performance of the miR2PE-score in two prospective plasma cohorts with AUROC of 0.933 and 0.787. Furthermore, the miR2PE-score revealed superior performance in non-invasive diagnosis compared with previously published miRNA biomarkers.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>We developed and validated a novel and robust blood-based miRNA signature, which may serve as a promising clinically applicable non-invasive tool for the early detection of PE.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical Abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1186\/s12916-022-02495-x","type":"journal-article","created":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T00:02:36Z","timestamp":1663027356000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["A blood-based miRNA signature for early non-invasive diagnosis of preeclampsia"],"prefix":"10.1186","volume":"20","author":[{"given":"Siqi","family":"Bao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congcong","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiale","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Chao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangye","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,9,13]]},"reference":[{"issue":"7","key":"2495_CR1","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1016\/S0026-0495(99)90225-1","volume":"48","author":"R Kaaja","year":"1999","unstructured":"Kaaja R, Laivuori H, Laakso M, Tikkanen M, Ylikorkala O. 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GEO https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE206988. 2022."}],"container-title":["BMC Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12916-022-02495-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12916-022-02495-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12916-022-02495-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T00:03:19Z","timestamp":1663027399000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmedicine.biomedcentral.com\/articles\/10.1186\/s12916-022-02495-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,13]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["2495"],"URL":"https:\/\/doi.org\/10.1186\/s12916-022-02495-x","relation":{},"ISSN":["1741-7015"],"issn-type":[{"value":"1741-7015","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,13]]},"assertion":[{"value":"28 April 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 July 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 September 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The current study was approved by the human ethics committee at the Second Affiliated Hospital and Yuying Children\u2019s Hospital of Wenzhou Medical University (approval number: LCKY2020-242), and informed consent was obtained from all patients and their families. And the study was performed in accordance with the regulations and guidelines established by this committee.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"303"}}