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Title: Functional PTGS2 polymorphism-based models as novel predictive markers in metastatic renal cell carcinoma patients receiving first-line sunitinib.
Authors: Cebrián, Arancha
Gómez Del Pulgar, Teresa
Méndez-Vidal, María José
Gonzálvez, María Luisa
Lainez, Nuria
Castellano, Daniel
García-Carbonero, Iciar
Esteban, Emilio
Sáez, Maria Isabel
Villatoro, Rosa
Suárez, Cristina
Carrato, Alfredo
Munárriz-Ferrándiz, Javier
Basterrechea, Laura
García-Alonso, Mirta
González-Larriba, José Luis
Perez-Valderrama, Begoña
Cruz-Jurado, Josefina
González Del Alba, Aránzazu
Moreno, Fernando
Reynés, Gaspar
Rodríguez-Remírez, María
Boni, Valentina
Mahillo-Fernández, Ignacio
Martin, Yolanda
Viqueira, Andrea
García-Foncillas, Jesús
metadata.dc.subject.mesh: Adult
Aged, 80 and over
Biomarkers, Tumor
Carcinoma, Renal Cell
Cyclooxygenase 2
Disease-Free Survival
Gene Frequency
Genetic Association Studies
Kaplan-Meier Estimate
Kidney Neoplasms
Middle Aged
Models, Genetic
Multivariate Analysis
Polymorphism, Single Nucleotide
Treatment Outcome
Issue Date: 24-Jan-2017
Abstract: 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.
metadata.dc.identifier.doi: 10.1038/srep41371
Appears in Collections:Producción 2020

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