Cebrian, AranchaGomez-Del-Pulgar, TeresaMendez-Vidal, Maria JoseGonzalvez, Maria LuisaLainez, NuriaCastellano, DanielGarcia-Carbonero, IciarEsteban, EmilioSaez, Maria IsabelVillatoro, RosaSuarez, CristinaCarrato, AlfredoMunarriz-Ferrandiz, JavierBasterrechea, LauraGarcia-Alonso, MirtaGonzalez-Larriba, Jose LuisPerez-Valderrama, BegoñaCruz-Jurado, JosefinaGonzalez-Del-Alba, AránzazuMoreno, FernandoReynes, GasparRodriguez-Remirez, MariaBoni, ValentinaMahillo-Fernandez, IgnacioMartin, YolandaViqueira, AndreaGarcia-Foncillas, Jesus2023-01-252023-01-252017-01-24Cebrián A, Gómez Del Pulgar T, Méndez-Vidal MJ, Gonzálvez ML, 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;7:41371http://hdl.handle.net/10668/10802Sunitinib 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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Biomarkers, TumorCarcinoma, Renal CellCyclooxygenase 2Disease-Free SurvivalGene FrequencyAdultAgedAged, 80 and overFemaleGenetic Association StudiesHumansIndolesKaplan-Meier EstimateKidney NeoplasmsMaleMiddle AgedModels, GeneticMultivariate AnalysisPolymorphism, Single NucleotidePyrrolesSunitinibTreatment Outcomeresearch article28117391open accessCarcinoma de células renales metastásicoPolimorfismo genéticoSupervivencia específica por cáncerProgresión libre de enfermedadBiomarcadores predictivos10.1038/srep413712045-2322PMC5259767https://www.nature.com/articles/srep41371.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259767/pdf