{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T22:23:44Z","timestamp":1767047024166,"version":"build-2065373602"},"reference-count":63,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T00:00:00Z","timestamp":1623024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["PI18\/01219"],"award-info":[{"award-number":["PI18\/01219"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014139","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer","doi-asserted-by":"publisher","award":["CB16\/12\/00481"],"award-info":[{"award-number":["CB16\/12\/00481"]}],"id":[{"id":"10.13039\/501100014139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011776","name":"Instituto Portugu\u00eas de Oncologia do Porto","doi-asserted-by":"publisher","award":["PI 74-CBEG-CI-IPOP-19-2015"],"award-info":[{"award-number":["PI 74-CBEG-CI-IPOP-19-2015"]}],"id":[{"id":"10.13039\/501100011776","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002704","name":"Fundaci\u00f3n Cient\u00edfica Asociaci\u00f3n Espa\u00f1ola Contra el C\u00e1ncer","doi-asserted-by":"publisher","award":["PRDVA18013LLUC","PRDVA19016LAME"],"award-info":[{"award-number":["PRDVA18013LLUC","PRDVA19016LAME"]}],"id":[{"id":"10.13039\/501100002704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008963","name":"Sociedad Espa\u00f1ola de Oncolog\u00eda M\u00e9dica","doi-asserted-by":"publisher","award":["R\u00edo Hortega-SEOM"],"award-info":[{"award-number":["R\u00edo Hortega-SEOM"]}],"id":[{"id":"10.13039\/501100008963","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The early diagnosis of breast cancer is essential to improve patients\u2019 survival rate. In this context, microRNAs have been described as potential diagnostic biomarkers for breast cancer. Particularly, circulating microRNAs have a strong value as non-invasive biomarkers. Herein, we assessed the potential of a microRNA signature based on miR-30b-5p and miR-99a-5p levels in plasma as a diagnostic biomarker for breast cancer. This two-microRNA signature was constructed by Principal Component Analysis and its prognostic value was assessed in a discovery cohort and blindly validated in a second cohort from an independent institution. ROC curve analysis and biomarker performance parameter evaluation demonstrated that our proposed signature presents a high value as a non-invasive biomarker for very early detection of breast cancer. In addition, pathway enrichment analysis identified three of the well-known pathways involved in cancer as targets of the two microRNAs.<\/jats:p>","DOI":"10.3390\/cancers13112848","type":"journal-article","created":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T13:25:43Z","timestamp":1623072343000},"page":"2848","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Identification of a Two-MicroRNA Signature in Plasma as a Novel Biomarker for Very Early Diagnosis of Breast Cancer"],"prefix":"10.3390","volume":"13","author":[{"given":"Anna","family":"Adam-Artigues","sequence":"first","affiliation":[{"name":"Oncology Department, Biomedical Research Institute INCLIVA, 46010 Valencia, Spain"}]},{"given":"Iris","family":"Garrido-Cano","sequence":"additional","affiliation":[{"name":"Oncology Department, Biomedical Research Institute INCLIVA, 46010 Valencia, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8449-5674","authenticated-orcid":false,"given":"Juan Antonio","family":"Carbonell-Asins","sequence":"additional","affiliation":[{"name":"Oncology Department, Biomedical Research Institute INCLIVA, 46010 Valencia, Spain"},{"name":"Precision Medicine Unit, INCLIVA, 46010 Valencia, Spain"},{"name":"Bioinformatics and Biostatistics Unit, INCLIVA, 46010 Valencia, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0441-6356","authenticated-orcid":false,"given":"Ana","family":"Lameirinhas","sequence":"additional","affiliation":[{"name":"Oncology Department, Biomedical Research Institute INCLIVA, 46010 Valencia, Spain"}]},{"given":"Soraya","family":"Sim\u00f3n","sequence":"additional","affiliation":[{"name":"Oncology Department, Biomedical Research Institute INCLIVA, 46010 Valencia, Spain"},{"name":"Clinical Oncology Department, Hospital Cl\u00ednico Universitario de Valencia, 46010 Valencia, Spain"}]},{"given":"Bel\u00e9n","family":"Ortega-Morillo","sequence":"additional","affiliation":[{"name":"Oncology Department, Biomedical Research Institute INCLIVA, 46010 Valencia, Spain"},{"name":"Clinical Oncology Department, Hospital Cl\u00ednico Universitario de Valencia, 46010 Valencia, Spain"}]},{"given":"Mar\u00eda Teresa","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Oncology Department, Biomedical Research Institute INCLIVA, 46010 Valencia, Spain"},{"name":"Clinical Oncology Department, Hospital Cl\u00ednico Universitario de Valencia, 46010 Valencia, Spain"}]},{"given":"Cristina","family":"Hernando","sequence":"additional","affiliation":[{"name":"Oncology Department, Biomedical Research Institute INCLIVA, 46010 Valencia, Spain"},{"name":"Clinical Oncology Department, Hospital Cl\u00ednico Universitario de Valencia, 46010 Valencia, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3151-0367","authenticated-orcid":false,"given":"Vera","family":"Const\u00e2ncio","sequence":"additional","affiliation":[{"name":"Cancer Biology and Epigenetics Group Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), 4200-072 Porto, Portugal"}]},{"given":"Octavio","family":"Burgues","sequence":"additional","affiliation":[{"name":"Oncology Department, Biomedical Research Institute INCLIVA, 46010 Valencia, Spain"},{"name":"Clinical Oncology Department, Hospital Cl\u00ednico Universitario de Valencia, 46010 Valencia, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), 28029 Madrid, Spain"}]},{"given":"Bego\u00f1a","family":"Bermejo","sequence":"additional","affiliation":[{"name":"Oncology Department, Biomedical Research Institute INCLIVA, 46010 Valencia, Spain"},{"name":"Clinical Oncology Department, Hospital Cl\u00ednico Universitario de Valencia, 46010 Valencia, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), 28029 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3171-4666","authenticated-orcid":false,"given":"Rui","family":"Henrique","sequence":"additional","affiliation":[{"name":"Cancer Biology and Epigenetics Group Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), 4200-072 Porto, Portugal"},{"name":"Department of Pathology, Portuguese Oncology Institute of Porto, 4200-072 Porto, Portugal"},{"name":"Department of Pathology and Molecular Immunology, School of Medical & Biomedical Sciences (ICBAS)-University of Porto, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2766-407X","authenticated-orcid":false,"given":"Ana","family":"Lluch","sequence":"additional","affiliation":[{"name":"Clinical Oncology Department, Hospital Cl\u00ednico Universitario de Valencia, 46010 Valencia, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), 28029 Madrid, Spain"},{"name":"Department of Medicine, Universitat de Val\u00e8ncia, 46010 Valencia, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4186-5345","authenticated-orcid":false,"given":"Carmen","family":"Jer\u00f3nimo","sequence":"additional","affiliation":[{"name":"Cancer Biology and Epigenetics Group Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), 4200-072 Porto, Portugal"},{"name":"Department of Pathology, Portuguese Oncology Institute of Porto, 4200-072 Porto, Portugal"},{"name":"Department of Pathology and Molecular Immunology, School of Medical & Biomedical Sciences (ICBAS)-University of Porto, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2708-6206","authenticated-orcid":false,"given":"Pilar","family":"Eroles","sequence":"additional","affiliation":[{"name":"Oncology Department, Biomedical Research Institute INCLIVA, 46010 Valencia, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), 28029 Madrid, Spain"},{"name":"Department of Physiology, Universitat de Val\u00e8ncia, 46010 Valencia, Spain"}]},{"given":"Juan Miguel","family":"Cejalvo","sequence":"additional","affiliation":[{"name":"Oncology Department, Biomedical Research Institute INCLIVA, 46010 Valencia, Spain"},{"name":"Clinical Oncology Department, Hospital Cl\u00ednico Universitario de Valencia, 46010 Valencia, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), 28029 Madrid, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,7]]},"reference":[{"key":"ref_1","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. 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