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oai:repisalud.isciii.es:20.500.12105/204052024-11-28T23:21:47Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967

00925njm 22002777a 4500 dc Cebrian, Arancha author Gomez del Pulgar, Teresa author Jose Mendez-Vidal, Maria author Luisa Gonzalvez, Maria author Lainez, Nuria author Castellano, Daniel author Garcia-Carbonero, Iciar author Esteban, Emilio author Isabel Saez, Maria author Villatoro, Rosa author Suarez, Cristina author Carrato, Alfredo author Munarriz-Ferrandiz, Javier author Basterrechea, Laura author Garcia-Alonso, Mirta author Luis Gonzalez-Larriba, Jose author Perez-Valderrama, Begona author Cruz-Jurado, Josefina author Gonzalez del Alba, Aranzazu author Moreno, Fernando author Reynes, Gaspar author Rodriguez-Remirez, Maria author Boni, Valentina author Mahillo-Fernandez, Ignacio author Martin, Yolanda author Viqueira, Andrea author Garcia-Foncillas, Jesus author 2017-01-24 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. 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. 10.1038/srep41371 2045-2322 Scientific Reports http://hdl.handle.net/20.500.13003/9981 28117391 L624523881 2-s2.0-85010973193 http://hdl.handle.net/20.500.12105/20405 392482800001 Functional PTGS2 polymorphism-based models as novel predictive markers in metastatic renal cell carcinoma patients receiving first-line sunitinib