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Título
Prospective study assessing hypoxia-related proteins as markers for the outcome of treatment with sunitinib in advanced clear-cell renal cell carcinoma.
Autor(es)
Garcia-Donas, J | Leandro-García, L J | González Del Alba, A | Morente, M | Alemany, I | Esteban, E | Arranz, J A | Climent, M A | Gallardo, E | Castellano, D E | Bellmunt, J | Mellado, B | Puente, J | Moreno, F | Font, A | Hernando, S | Robledo Batanero, Mercedes CNIO | Rodriguez Antona, Cristina CNIO
Fecha de publicación
2013-09
Cita
Ann Oncol . 2013;24(9):2409-14.
Idioma
Inglés
Tipo de documento
journal article
Resumen
BACKGROUND
Previous studies suggest that expression of hypoxia markers may be associated with response to antiangiogenic drugs. Thus, we aimed to identify predictors of sunitinib outcome in clear-cell renal cell carcinoma (ccRCC).
PATIENTS AND METHODS
The expression of eight key proteins related to hypoxia (CAIX, HIF1A, HIF2A, VEGFA, VEGFR1, VEGFR2, VEGFR3 and PDGFRB) and P-glycoprotein were assessed by immunohistochemistry in 67 primary ccRCC samples from prospectively recruited patients treated with first-line sunitinib. The proteins expression, VHL inactivation and EGLN3 mRNA content were compared with the patients' response to sunitinib.
RESULTS
High expression of HIF2A and PDGFRB was associated with better sunitinib RECIST objective response (P = 0.024 and P = 0.026; respectively) and increased VEGFR3 expression was associated with longer progression-free survival (P = 0.012). VEGFR3 overexpression showed a negative correlation with VEGFR3 polymorphism rs307826 (P = 0.002), a sunitinib resistance predictor. With respect to overall survival (OS), high VEGFA was associated with short (P = 0.009) and HIF2A with long (P = 0.048) survival times. High EGLN3 mRNA content was associated with shorter OS (P = 0.023).
CONCLUSIONS
We found an association between several proteins involved in hypoxia and sunitinib efficacy. In addition, low VEGFR3 expression was associated with worse outcome and with VEGFR3 rs307826 variant allele, reinforcing VEGFR3 as a marker of sunitinib resistance.
MESH
Aged | Aged, 80 and over | Angiogenesis Inhibitors | Antineoplastic Agents | Basic Helix-Loop-Helix Transcription Factors | Biomarkers, Tumor | Carcinoma, Renal Cell | Cell Hypoxia | Disease-Free Survival | Drug Resistance, Neoplasm | Female | Gene Expression | Humans | Hypoxia-Inducible Factor-Proline Dioxygenases | Immunohistochemistry | Indoles | Kidney Neoplasms | Male | Middle Aged | Neoplasm Metastasis | Prospective Studies | Pyrroles | RNA, Messenger | Sunitinib | Survival | Treatment Outcome | Vascular Endothelial Growth Factor Receptor-3
Versión en línea
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