title: Validation of VEGFR1 rs9582036 as predictive biomarker in metastatic clear-cell renal cell carcinoma patients treated with sunitinib.
abstract: OBJECTIVE
  To validate vascular endothelial growth factor receptor-1 (VEGFR1) single nucleotide polymorphism (SNP) rs9582036 as a potential predictive biomarker in metastatic clear-cell renal cell carcinoma (m-ccRCC) patients treated with sunitinib.
  
  
  METHODS
  m-ccRCC patients receiving sunitinib as first-line targeted therapy were included. We assessed response rate (RR), progression-free survival (PFS), overall survival (OS), and clinical and biochemical parameters associated with outcome. We genotyped five VEGFR1 SNPs: rs9582036, rs7993418, rs9554320, rs9554316 and rs9513070. Association with outcome was studied by univariate analysis and by multivariate Cox regression. Additionally, we updated survival data of our discovery cohort as described previously.
  
  
  RESULTS
  Sixty-nine patients were included in the validation cohort. rs9582036 CC-carriers had a poorer PFS (8 vs 12 months, P = 0.02) and OS (11 vs 27 months, P = 0.003) compared to AC/AA-carriers. rs7993418 CC-carriers had a poorer OS (8 vs 24 months, P = 0.004) compared to TC/TT-carriers. rs9554320 AA-carriers had a poorer RR (0% vs 53%, P = 0.009), PFS (5 vs 12 months, P = 0.003) and OS (10 vs 25 months, P = 0.004) compared to AC/CC-carriers. When pooling patients from the discovery cohort, as described previously (n = 88), and the validation cohort, in the total series of 157 patients, rs9582036 CC-carriers had a poorer RR (8% vs 49%, P = 0.004), PFS (8 vs 14 months, P = 0.003) and OS (13 vs 30 months, P = 0.0004) compared to AC/AA-carriers. Unfavorable prognostic markers at start of sunitinib were well balanced between rs9582036 CC- and AC/AA-carriers.
  
  
  CONCLUSIONS
  VEGFR1 rs9582036 is a candidate predictive biomarker in m-ccRCC-patients treated with sunitinib.
authors.affiliation: Inserm, UMR-1162, Génomique fonctionnelle des tumeurs solides, IUH, Paris, France.|Sorbonne Paris Cité, Faculté de Médecine, Université Paris Descartes, Paris, France.|Department of General Medical Oncology and Laboratory for Experimental Oncology, University Hospitals Leuven, Leuven Cancer Institute, KU Leuven, Leuven, Belgium.
authors.forename: Benoit
authors.initials: B
authors.lastname: Beuselinck
authors.affiliation: Inserm, UMR-1162, Génomique fonctionnelle des tumeurs solides, IUH, Paris, France.|Sorbonne Paris Cité, Faculté de Médecine, Université Paris Descartes, Paris, France.
authors.forename: Johnny
authors.initials: J
authors.lastname: Jean-Baptiste
authors.affiliation: Department of General Medical Oncology and Laboratory for Experimental Oncology, University Hospitals Leuven, Leuven Cancer Institute, KU Leuven, Leuven, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schöffski
authors.affiliation: Inserm, UMR-1162, Génomique fonctionnelle des tumeurs solides, IUH, Paris, France.|Sorbonne Paris Cité, Faculté de Médecine, Université Paris Descartes, Paris, France.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Couchy
authors.affiliation: Inserm, UMR-1162, Génomique fonctionnelle des tumeurs solides, IUH, Paris, France.|Sorbonne Paris Cité, Faculté de Médecine, Université Paris Descartes, Paris, France.
authors.forename: Clément
authors.initials: C
authors.lastname: Meiller
authors.affiliation: Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Saint Herblain, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Rolland
authors.affiliation: Department of Pathology, Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Créteil, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Allory
authors.affiliation: Department of Urology, University Hospitals Leuven, Leuven Cancer Institute, KU Leuven, Leuven, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Joniau
authors.affiliation: Department of Pathology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants malades, Paris, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Verkarre
authors.affiliation: Department of Medical Oncology, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: Reza
authors.initials: R
authors.lastname: Elaidi
authors.affiliation: Department of Pathology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Lerut
authors.affiliation: Department of Pathology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Tania
authors.initials: T
authors.lastname: Roskams
authors.affiliation: Department of Urology, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Patard
authors.affiliation: Sorbonne Paris Cité, Faculté de Médecine, Université Paris Descartes, Paris, France.|Department of Medical Oncology, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Oudard
authors.affiliation: Department of Urology, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Méjean
authors.affiliation: Laboratory for Translational Genetics, Department of Oncology, KU Leuven, Leuven, Belgium.|Vesalius Research Center, VIB, Leuven, Belgium.
authors.forename: Diether
authors.initials: D
authors.lastname: Lambrechts
authors.affiliation: Inserm, UMR-1162, Génomique fonctionnelle des tumeurs solides, IUH, Paris, France.|Sorbonne Paris Cité, Faculté de Médecine, Université Paris Descartes, Paris, France.|Department of Medical Oncology, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: Jessica
authors.initials: J
authors.lastname: Zucman-Rossi
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics* / Q000556:secondary; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011758:Pyrroles / Q000627:therapeutic use*; D012189:Retrospective Studies; D000077210:Sunitinib; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007211:Indoles; D011758:Pyrroles; D040281:Vascular Endothelial Growth Factor Receptor-1; D000077210:Sunitinib
keywords: VEGFR1; clear-cell renal cell carcinoma; polymorphisms; predictive factors; sunitinib