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Functional PTGS2 polymorphism-based models as novel predictive markers in metastatic renal cell carcinoma patients receiving first-line sunitinib.

dc.contributor.authorCebrián, Arancha
dc.contributor.authorGómez Del Pulgar, Teresa
dc.contributor.authorMéndez-Vidal, María José
dc.contributor.authorGonzálvez, María Luisa
dc.contributor.authorLainez, Nuria
dc.contributor.authorCastellano, Daniel
dc.contributor.authorGarcía-Carbonero, Iciar
dc.contributor.authorEsteban, Emilio
dc.contributor.authorSáez, Maria Isabel
dc.contributor.authorVillatoro, Rosa
dc.contributor.authorSuárez, Cristina
dc.contributor.authorCarrato, Alfredo
dc.contributor.authorMunárriz-Ferrándiz, Javier
dc.contributor.authorBasterrechea, Laura
dc.contributor.authorGarcía-Alonso, Mirta
dc.contributor.authorGonzález-Larriba, José Luis
dc.contributor.authorPerez-Valderrama, Begoña
dc.contributor.authorCruz-Jurado, Josefina
dc.contributor.authorGonzález Del Alba, Aránzazu
dc.contributor.authorMoreno, Fernando
dc.contributor.authorReynés, Gaspar
dc.contributor.authorRodríguez-Remírez, María
dc.contributor.authorBoni, Valentina
dc.contributor.authorMahillo-Fernández, Ignacio
dc.contributor.authorMartin, Yolanda
dc.contributor.authorViqueira, Andrea
dc.contributor.authorGarcía-Foncillas, Jesús
dc.date.accessioned2023-01-25T09:43:08Z
dc.date.available2023-01-25T09:43:08Z
dc.date.issued2017-01-24
dc.description.abstractSunitinib 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.
dc.identifier.doi10.1038/srep41371
dc.identifier.essn2045-2322
dc.identifier.pmcPMC5259767
dc.identifier.pmid28117391
dc.identifier.pubmedURLhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259767/pdf
dc.identifier.unpaywallURLhttps://www.nature.com/articles/srep41371.pdf
dc.identifier.urihttp://hdl.handle.net/10668/10802
dc.journal.titleScientific reports
dc.journal.titleabbreviationSci Rep
dc.language.isoen
dc.organizationHospital Universitario Reina Sofía
dc.organizationHospital Universitario Virgen de la Victoria
dc.organizationHospital Costa del Sol
dc.organizationHospital Universitario Virgen del Rocío
dc.page.number41371
dc.pubmedtypeJournal Article
dc.pubmedtypeMulticenter Study
dc.pubmedtypeObservational Study
dc.pubmedtypeResearch Support, Non-U.S. Gov't
dc.rightsAttribution 4.0 International
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAged, 80 and over
dc.subject.meshBiomarkers, Tumor
dc.subject.meshCarcinoma, Renal Cell
dc.subject.meshCyclooxygenase 2
dc.subject.meshDisease-Free Survival
dc.subject.meshFemale
dc.subject.meshGene Frequency
dc.subject.meshGenetic Association Studies
dc.subject.meshHumans
dc.subject.meshIndoles
dc.subject.meshKaplan-Meier Estimate
dc.subject.meshKidney Neoplasms
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshModels, Genetic
dc.subject.meshMultivariate Analysis
dc.subject.meshPolymorphism, Single Nucleotide
dc.subject.meshPyrroles
dc.subject.meshSunitinib
dc.subject.meshTreatment Outcome
dc.titleFunctional PTGS2 polymorphism-based models as novel predictive markers in metastatic renal cell carcinoma patients receiving first-line sunitinib.
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number7
dspace.entity.typePublication
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