Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/17506
Título
Deep sequencing reveals microRNAs predictive of antiangiogenic drug response.
Autor(es)
García-Donas, Jesús | Beuselinck, Benoit | Inglada-Pérez, Lucía | Graña, Osvaldo | Schöffski, Patrick | Wozniak, Agnieszka | Bechter, Oliver | Apellániz-Ruiz, Maria | Leandro-García, Luis Javier | Esteban, Emilio | Castellano, Daniel E | González Del Alba, Aranzazu | Climent, Miguel Angel | Hernando, Susana | Arranz, José Angel | Morente, Manuel | Pisano, David G | Rodriguez Antona, Cristina CNIO | Robledo, Mercedes
Fecha de publicación
2016-07-07
Cita
JCI Insight . 2016 ;1(10):e86051.
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
MESH
Adult | Aged | Aged, 80 and over | Angiogenesis Inhibitors | Carcinoma, Renal Cell | Disease-Free Survival | Female | Gene Expression Regulation, Neoplastic | High-Throughput Nucleotide Sequencing | Humans | Kidney Neoplasms | Male | MicroRNAs | Middle Aged | Protein Kinase Inhibitors | Survival Rate
Versión en línea
DOI
Aparece en las colecciones
Ficheros en el ítem
- Nombre:
- DeepsequencingrevealsmicroRNAs ...
- Tamaño:
- 497.2Kb
- Formato:
- Descripción:
- Artículo principal