2026-06-14T03:54:20Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/175062024-11-29T19:53:43Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc García-Donas, Jesús author Beuselinck, Benoit author Inglada-Pérez, Lucía author Graña, Osvaldo author Schöffski, Patrick author Wozniak, Agnieszka author Bechter, Oliver author Apellániz-Ruiz, Maria author Leandro-García, Luis Javier author Esteban, Emilio author Castellano, Daniel E author González Del Alba, Aranzazu author Climent, Miguel Angel author Hernando, Susana author Arranz, José Angel author Morente, Manuel author Pisano, David G author Rodriguez Antona, Cristina author Robledo, Mercedes author 2016-07-07 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 (P values from 6 × 10-9 to 3 × 10-3). Among 6 miRNAs selected for validation in an independent series, the most relevant associations corresponded to miR-1307-3p, miR-155-5p, and miR-221-3p (P = 4.6 × 10-3, 6.5 × 10-3, and 3.4 × 10-2, respectively). Furthermore, a 2 miRNA-based classifier discriminated individuals with progressive disease upon TKI treatment (AUC = 0.75, 95% CI, 0.64-0.85; P = 1.3 × 10-4) with better predictive value than clinicopathological risk factors commonly used. We also identified miRNAs significantly associated with progression-free survival and overall survival (P = 6.8 × 10-8 and 7.8 × 10-7 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. JCI Insight . 2016 ;1(10):e86051. 10.1172/jci.insight.86051 2379-3708 JCI insight 27699216 http://hdl.handle.net/20.500.12105/17506 Deep sequencing reveals microRNAs predictive of antiangiogenic drug response.