RT Journal Article
T1 Functional PTGS2 polymorphism-based models as novel predictive markers in metastatic renal cell carcinoma patients receiving first-line sunitinib.
A1 Cebrián, Arancha
A1 Gómez Del Pulgar, Teresa
A1 Méndez-Vidal, María José
A1 Gonzálvez, María Luisa
A1 Lainez, Nuria
A1 Castellano, Daniel
A1 García-Carbonero, Iciar
A1 Esteban, Emilio
A1 Sáez, Maria Isabel
A1 Villatoro, Rosa
A1 Suárez, Cristina
A1 Carrato, Alfredo
A1 Munárriz-Ferrándiz, Javier
A1 Basterrechea, Laura
A1 García-Alonso, Mirta
A1 González-Larriba, José Luis
A1 Perez-Valderrama, Begoña
A1 Cruz-Jurado, Josefina
A1 González Del Alba, Aránzazu
A1 Moreno, Fernando
A1 Reynés, Gaspar
A1 Rodríguez-Remírez, María
A1 Boni, Valentina
A1 Mahillo-Fernández, Ignacio
A1 Martin, Yolanda
A1 Viqueira, Andrea
A1 García-Foncillas, Jesús
AB 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.
YR 2017
FD 2017-01-24
LK http://hdl.handle.net/10668/10802
UL http://hdl.handle.net/10668/10802
LA en
DS RISalud
RD Apr 5, 2025