{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T15:08:20Z","timestamp":1779203300928,"version":"3.51.4"},"reference-count":51,"publisher":"American Society for Clinical Investigation","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,7,7]]},"abstract":"<jats:p>\n                    The majority of metastatic renal cell carcinoma (RCC) patients are treated with tyrosine kinase inhibitors (TKI) in first-line treatment; however, a fraction are refractory to these antiangiogenic drugs. MicroRNAs (miRNAs) are regulatory molecules proven to be accurate biomarkers in cancer. Here, we identified miRNAs predictive of progressive disease under TKI treatment through deep sequencing of 74 metastatic clear cell RCC cases uniformly treated with these drugs. Twenty-nine miRNAs were differentially expressed in the tumors of patients who progressed under TKI therapy (\n                    <jats:italic>P<\/jats:italic>\n                    values from 6 \u00d7 10\n                    <jats:sup>\u20139<\/jats:sup>\n                    to 3 \u00d7 10\n                    <jats:sup>\u20133<\/jats:sup>\n                    ). Among 6 miRNAs selected for validation in an independent series, the most relevant associations corresponded to miR\u20131307-3p, miR\u2013155-5p, and miR\u2013221-3p (\n                    <jats:italic>P<\/jats:italic>\n                    = 4.6 \u00d7 10\n                    <jats:sup>\u20133<\/jats:sup>\n                    , 6.5 \u00d7 10\n                    <jats:sup>\u20133<\/jats:sup>\n                    , and 3.4 \u00d7 10\n                    <jats:sup>\u20132<\/jats:sup>\n                    , respectively). Furthermore, a 2 miRNA\u2013based classifier discriminated individuals with progressive disease upon TKI treatment (AUC = 0.75, 95% CI, 0.64\u20130.85;\n                    <jats:italic>P<\/jats:italic>\n                    = 1.3 \u00d7 10\n                    <jats:sup>\u20134<\/jats:sup>\n                    ) with better predictive value than clinicopathological risk factors commonly used. We also identified miRNAs significantly associated with progression-free survival and overall survival (\n                    <jats:italic>P<\/jats:italic>\n                    = 6.8 \u00d7 10\n                    <jats:sup>\u20138<\/jats:sup>\n                    and 7.8 \u00d7 10\n                    <jats:sup>\u20137<\/jats:sup>\n                    for top hits, respectively), and 7 overlapped with early progressive disease. In conclusion, this is the first miRNome comprehensive study, to our knowledge, that demonstrates a predictive value of miRNAs for TKI response and provides a new set of relevant markers that can help rationalize metastatic RCC treatment.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.86051","type":"journal-article","created":{"date-parts":[[2016,7,6]],"date-time":"2016-07-06T11:00:57Z","timestamp":1467802857000},"source":"Crossref","is-referenced-by-count":36,"title":["Deep sequencing reveals microRNAs predictive of antiangiogenic drug response"],"prefix":"10.1172","volume":"1","author":[{"given":"Jes\u00fas","family":"Garc\u00eda-Donas","sequence":"first","affiliation":[{"name":"Oncology Unit, HM Hospitales - Centro Integral Oncol\u00f3gico HM Clara Campal, Madrid, Spain."},{"name":"Spanish Oncology Genitourinary Group, Madrid, 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