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Título
Functional PTGS2 polymorphism-based models as novel predictive markers in metastatic renal cell carcinoma patients receiving first-line sunitinib
Autor(es)
Cebrian, Arancha | Gomez del Pulgar, Teresa | Jose Mendez-Vidal, Maria | Luisa Gonzalvez, Maria | Lainez, Nuria | Castellano, Daniel | Garcia-Carbonero, Iciar | Esteban, Emilio | Isabel Saez, Maria | Villatoro, Rosa | Suarez, Cristina | Carrato, Alfredo | Munarriz-Ferrandiz, Javier | Basterrechea, Laura | Garcia-Alonso, Mirta | Luis Gonzalez-Larriba, Jose | Perez-Valderrama, Begona | Cruz-Jurado, Josefina | Gonzalez del Alba, Aranzazu | Moreno, Fernando | Reynes, Gaspar | Rodriguez-Remirez, Maria | Boni, Valentina | Mahillo-Fernandez, Ignacio ISCIII | Martin, Yolanda | Viqueira, Andrea | Garcia-Foncillas, Jesus
Fecha de publicación
2017-01-24
Cita
Cebrian A, Gomez Del Pulgar T, Mendez-Vidal MJ, Luisa Gonzalvez M, Lainez N, Castellano D, et al. Functional PTGS2 polymorphism-based models as novel predictive markers in metastatic renal cell carcinoma patients receiving first-line sunitinib. Sci Rep. 2017 Jan 24;7:41371.
Idioma
Inglés
Tipo de documento
research article
Resumen
Sunitinib is the currently standard treatment for metastatic renal cell carcinoma (mRCC). Multiple candidate predictive biomarkers for sunitinib response have been evaluated but none of them has been implemented in the clinic yet. The aim of this study was to analyze single nucleotide polymorphisms (SNPs) in genes linked to mode of action of sunitinib and immune response as biomarkers for mRCC. This is a multicenter, prospective and observational study involving 20 hospitals. Seventy-five mRCC patients treated with sunitinib as first line were used to assess the impact of 63 SNPs in 31 candidate genes on clinical outcome. rs2243250 (IL4) and rs5275 (PTGS2) were found to be significantly associated with shorter cancer-specific survival (CSS). Moreover, allele C (rs5275) was associated with higher PTGS2 expression level confirming its functional role. Combination of rs5275 and rs7651265 or rs2243250 for progression free survival (PFS) or CSS, respectively, was a more valuable predictive biomarker remaining significant after correction for multiple testing. It is the first time that association of rs5275 with survival in mRCC patients is described. Two-SNP models containing this functional variant may serve as more predictive biomarkers for sunitinib and could suppose a clinically relevant tool to improve the mRCC patient management.
MESH
Disease-Free Survival | Aged, 80 and over | Aged | Kaplan-Meier Estimate | Adult | Gene Frequency | Models, Genetic | Humans | Middle Aged | Polymorphism, Single Nucleotide | Carcinoma, Renal Cell | Indoles | Male | Multivariate Analysis | Kidney Neoplasms | Biomarkers, Tumor | Female | Pyrroles | Treatment Outcome | Genetic Association Studies | Cyclooxygenase 2
DECS
Resultado del Tratamiento | Polimorfismo de Nucleótido Simple | Femenino | Análisis Multivariante | Indoles | Biomarcadores de Tumor | Carcinoma de Células Renales | Neoplasias Renales | Masculino | Modelos Genéticos | Pirroles | Humanos | Persona de Mediana Edad | Frecuencia de los Genes | Estudios de Asociación Genética | Estimación de Kaplan-Meier | Anciano | Anciano de 80 o más Años | Ciclooxigenasa 2 | Adulto | Supervivencia sin Enfermedad
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