{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T12:23:37Z","timestamp":1772367817742,"version":"3.50.1"},"reference-count":88,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,22]],"date-time":"2024-06-22T00:00:00Z","timestamp":1719014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III (ISCIII), Spain","doi-asserted-by":"publisher","award":["PI23\/00907"],"award-info":[{"award-number":["PI23\/00907"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III (ISCIII), Spain","doi-asserted-by":"publisher","award":["2023333023"],"award-info":[{"award-number":["2023333023"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III (ISCIII), Spain","doi-asserted-by":"publisher","award":["2023333040"],"award-info":[{"award-number":["2023333040"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III (ISCIII), Spain","doi-asserted-by":"publisher","award":["KK-2023\/00001"],"award-info":[{"award-number":["KK-2023\/00001"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union, Departamento de Salud del Gobierno Vasco, Spain","award":["PI23\/00907"],"award-info":[{"award-number":["PI23\/00907"]}]},{"name":"European Union, Departamento de Salud del Gobierno Vasco, Spain","award":["2023333023"],"award-info":[{"award-number":["2023333023"]}]},{"name":"European Union, Departamento de Salud del Gobierno Vasco, Spain","award":["2023333040"],"award-info":[{"award-number":["2023333040"]}]},{"name":"European Union, Departamento de Salud del Gobierno Vasco, Spain","award":["KK-2023\/00001"],"award-info":[{"award-number":["KK-2023\/00001"]}]},{"name":"Departamento de Industria del Gobierno Vasco, Spain","award":["PI23\/00907"],"award-info":[{"award-number":["PI23\/00907"]}]},{"name":"Departamento de Industria del Gobierno Vasco, Spain","award":["2023333023"],"award-info":[{"award-number":["2023333023"]}]},{"name":"Departamento de Industria del Gobierno Vasco, Spain","award":["2023333040"],"award-info":[{"award-number":["2023333040"]}]},{"name":"Departamento de Industria del Gobierno Vasco, Spain","award":["KK-2023\/00001"],"award-info":[{"award-number":["KK-2023\/00001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sunitinib has greatly improved the survival of clear cell renal cell carcinoma (ccRCC) patients in recent years. However, 20\u201330% of treated patients do not respond. To identify miRNAs and genes associated with a response, comparisons were made between biopsies from responder and non-responder ccRCC patients. Using integrated transcriptomic analyses, we identified 37 miRNAs and 60 respective target genes, which were significantly associated with the NF-kappa B, PI3K-Akt and MAPK pathways. We validated expression of the miRNAs (miR-223, miR-155, miR-200b, miR-130b) and target genes (FLT1, PRDM1 and SAV1) in 35 ccRCC patients. High levels of miR-223 and low levels of FLT1, SAV1 and PRDM1 were associated with worse overall survival (OS), and combined miR-223 + SAV1 levels distinguished responders from non-responders (AUC = 0.92). Using immunohistochemical staining of 170 ccRCC patients, VEGFR1 (FLT1) expression was associated with treatment response, histological grade and RECIST (Response Evaluation Criteria in Solid Tumors) score, whereas SAV1 and BLIMP1 (PRDM1) were associated with metachronous metastatic disease. Using in situ hybridisation (ISH) to detect miR-155 we observed higher tumoural cell expression in non-responders, and non-tumoural cell expression with increased histological grade. In summary, our preliminary analysis using integrated miRNA-target gene analyses identified several novel biomarkers in ccRCC patients that surely warrant further investigation.<\/jats:p>","DOI":"10.3390\/ijms25136881","type":"journal-article","created":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T08:42:03Z","timestamp":1719218523000},"page":"6881","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Identification of miRNAs and Their Target Genes Associated with Sunitinib Resistance in Clear Cell Renal Cell Carcinoma Patients"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0185-3913","authenticated-orcid":false,"given":"Mar\u00eda","family":"Armesto","sequence":"first","affiliation":[{"name":"Molecular Oncology Group, Biogipuzkoa Health Research Institute, 20014 San Sebasti\u00e1n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0399-5213","authenticated-orcid":false,"given":"St\u00e9phane","family":"Nemours","sequence":"additional","affiliation":[{"name":"Molecular Oncology Group, Biogipuzkoa Health Research Institute, 20014 San Sebasti\u00e1n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2449-444X","authenticated-orcid":false,"given":"Mar\u00eda","family":"Arest\u00edn","sequence":"additional","affiliation":[{"name":"Molecular Oncology Group, Biogipuzkoa Health Research Institute, 20014 San Sebasti\u00e1n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6527-6951","authenticated-orcid":false,"given":"Iraide","family":"Bernal","sequence":"additional","affiliation":[{"name":"Molecular Oncology Group, Biogipuzkoa Health Research Institute, 20014 San Sebasti\u00e1n, Spain"},{"name":"Pathology Department, Donostia University Hospital, 20014 San Sebasti\u00e1n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jon Danel","family":"Solano-Iturri","sequence":"additional","affiliation":[{"name":"Pathology Department, Donostia University Hospital, 20014 San Sebasti\u00e1n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Manrique","sequence":"additional","affiliation":[{"name":"Pathology Department, Donostia University Hospital, 20014 San Sebasti\u00e1n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8450-713X","authenticated-orcid":false,"given":"Laura","family":"Basterretxea","sequence":"additional","affiliation":[{"name":"Molecular Oncology Group, Biogipuzkoa Health Research Institute, 20014 San Sebasti\u00e1n, Spain"},{"name":"Medical Oncology Department, Donostia University Hospital, 20014 San Sebasti\u00e1n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6744-818X","authenticated-orcid":false,"given":"Gorka","family":"Larrinaga","sequence":"additional","affiliation":[{"name":"Biobizkaia Health Research Institute, 48903 Barakaldo, Spain"},{"name":"Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV\/EHU), 48940 Leioa, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1735-8792","authenticated-orcid":false,"given":"Javier C.","family":"Angulo","sequence":"additional","affiliation":[{"name":"Clinical Department, Faculty of Medical Sciences, European University of Madrid, 28905 Getafe, Spain"},{"name":"Department of Urology, University Hospital of Getafe, 28907 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Lecumberri","sequence":"additional","affiliation":[{"name":"Department of Urology, Urduliz 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20014 San Sebasti\u00e1n, Spain"},{"name":"IKERBASQUE, Basque Foundation for Science, 48009 Bilbao, Spain"},{"name":"Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.ejca.2018.07.005","article-title":"Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018","volume":"103","author":"Ferlay","year":"2018","journal-title":"Eur. 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