Single nucleotide polymorphisms as prognostic and predictive biomarkers in renal cell carcinoma
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Carmen Garrigós1, Marta Espinosa1, Ana Salinas1, Ignacio Osman2, Rafael Medina2, Miguel Taron1, Sonia Molina-Pinelo1,3 and Ignacio Duran1
1Instituto de Biomedicina de Sevilla, IBiS, Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, Sevilla, Spain
2Unidad de Urología Oncológica, UGC Urología-Nefrología H.U.Virgen del Rocío, Instituto de Biomedicina de Sevilla, IBiS, Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, Sevilla, Spain
3Centro de Investigación Biomédica en Red Cáncer, CIBERONC, Madrid, Spain
Ignacio Duran, email: [email protected]
Keywords: single nucleotide polymorphisms; angiogenesis genes; biomarkers; localized renal cell carcinoma; advanced renal cell carcinoma
Received: May 13, 2017 Accepted: October 25, 2017 Published: November 20, 2017
Despite major advances in the knowledge of the molecular basis of renal cell carcinoma, prognosis is still defined using clinical and pathological parameters. Moreover, no valid predictive biomarkers exist to help us selecting the best treatment for each patient. With these premises, we aimed to analyse the expression and to determine the prognostic and predictive value of 64 key single nucleotide polymorphisms in 18 genes related with angiogenesis or metabolism of antiangiogenics in two cohorts of patients with localized and advanced renal cell cancer treated at our institution. The presence of the selected single nucleotide polymorphisms was correlated with clinical features, disease free survival, overall survival and response rate. In patients with localized renal cell cancer, 5 of these polymorphisms in 3 genes involved in angiogenesis predicted for worse disease free survival (VEGFR2: rs10013228; PDGFRA: rs2228230) or shorter overall survival (VEGFR2: rs10013228; VEGFR3: rs6877011, rs307826) (p < 0.05). Rs2071559 in VEGFR2 showed a protective effect (p = 0.01). In the advanced setting, 5 SNPs determined inferior overall survival (IL8: rs2227543, PRKAR1B: rs9800958, PDGFRB: rs2302273; p = 0.05) or worse response rate (VEGFA: rs699947, rs3025010 p ≤ 0.01)). Additionally 1 single nucleotide polymorphism in VEGFB predicted for better response rate rs594942 (p = 0.03). Genetic analysis of renal cell carcinoma patients might provide valuable prognostic/predictive information. A set of SNPs in genes critical to angiogenesis and metabolism of antiangiogenics drugs seem to determine post-surgical outcomes and treatment response in our series.
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