Garrigós Carmen, Espinosa Marta, Salinas Ana, Osman Ignacio, Medina Rafael, Taron Miguel, Molina-Pinelo Sonia, Duran Ignacio
Instituto de Biomedicina de Sevilla, IBiS, Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, Sevilla, Spain.
Unidad 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.
Oncotarget. 2017 Nov 20;8(63):106551-106564. doi: 10.18632/oncotarget.22533. eCollection 2017 Dec 5.
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) ( < 0.05). Rs2071559 in VEGFR2 showed a protective effect ( = 0.01). In the advanced setting, 5 SNPs determined inferior overall survival (IL8: rs2227543, PRKAR1B: rs9800958, PDGFRB: rs2302273; = 0.05) or worse response rate (VEGFA: rs699947, rs3025010 ≤ 0.01)). Additionally 1 single nucleotide polymorphism in VEGFB predicted for better response rate rs594942 ( = 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.
尽管在肾细胞癌分子基础的认识方面取得了重大进展，但预后仍通过临床和病理参数来界定。此外，不存在有效的预测生物标志物来帮助我们为每位患者选择最佳治疗方案。基于这些前提，我们旨在分析18个与血管生成或抗血管生成药物代谢相关基因中64个关键单核苷酸多态性的表达情况，并确定其在我们机构接受治疗的两组局限性和晚期肾细胞癌患者中的预后和预测价值。所选单核苷酸多态性的存在与临床特征、无病生存期、总生存期和缓解率相关。在局限性肾细胞癌患者中，参与血管生成的3个基因中的5个多态性预测无病生存期较差（VEGFR2：rs10013228；PDGFRA：rs2228230）或总生存期较短（VEGFR2：rs10013228；VEGFR3：rs6877011，rs307826）（<0.05）。VEGFR2中的Rs2071559显示出保护作用（=0.01）。在晚期病例中，5个单核苷酸多态性决定了较差的总生存期（IL8：rs2227543，PRKAR1B：rs9800958，PDGFRB：rs2302273；=0.05）或较差的缓解率（VEGFA：rs699947，rs3025010≤0.01）。此外，VEGFB中的1个单核苷酸多态性预测缓解率较好rs594942（=0.03）。肾细胞癌患者的基因分析可能提供有价值的预后/预测信息。一组对抗血管生成药物的血管生成和代谢至关重要的基因中的单核苷酸多态性似乎决定了我们系列中的术后结果和治疗反应。
