Evaluation of polymorphisms in angiogenesis-related genes as predictive and prognostic markers for sunitinib-treated metastatic renal cell carcinoma patients
Evaluation of polymorphisms in angiogenesis-related genes as predictive and prognostic markers for sunitinib-treated metastatic renal cell carcinoma patients
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DOI：
10.1007/s00432-016-2137-0
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发表时间：
2016-06-01
影响因子：
3.6
通讯作者：
Fuessel, Susanne
中科院分区：
文献类型：
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作者：
Dornbusch, Juana;Walter, Martina;Fuessel, Susanne
血管生成相关基因的单核苷酸多态性（snp）可能在酪氨酸激酶抑制剂舒尼替尼的活性中发挥重要作用，并可能影响使用该药物治疗的癌症患者的生存。这项回顾性研究的目的是阐明在转移性肾细胞癌（mRCC）患者独立队列中，VEGFA、VEGFR1、VEGFR2和VEGFR3中10个已知snp作为潜在预后和预测标志物的作用。121例接受舒尼替尼治疗的mRCC患者的DNA通过TaqMan基因分型分析snp。根据RECIST评估疾病控制率。从医疗记录中登记了舒尼替尼的不良反应。采用多重检验的校正方法对Cox回归和logistic回归结果进行验证。Kaplan-Meier分析显示，与变异等位基因相比，VEGFA SNP rs699947野生型（WT）等位基因患者的无进展生存期降低。具有VEGFR1 SNP rs9582036的AA/ ac等位基因的患者与具有CC-WT等位基因的患者相比，具有更高的中位总生存期，这可以通过多变量Cox比例风险回归分析来证实。分析的snp与较高的不良反应风险之间没有统计学上的显著关联。本研究结果表明，大多数选择的血管生成相关基因的snp与舒尼替尼治疗后mRCC患者的生存无关，也与不良反应无关。只有VEGFR1 SNP rs9582036与总生存率有统计学意义的关联。snp作为舒尼替治疗的mRCC患者预后和预测标志物的潜力最终应通过前瞻性研究进行评估。
Single nucleotide polymorphisms (SNPs) in angiogenesis-associated genes might play an important role in activity of the tyrosine kinase inhibitor sunitinib and could affect survival of cancer patients treated with this drug. The aim of this retrospective study was to elucidate the role of 10 known SNPs in VEGFA, VEGFR1, VEGFR2 and VEGFR3 as potential prognostic and predictive markers in an independent cohort of patients with metastatic renal cell carcinoma (mRCC).DNA from 121 mRCC patients treated with sunitinib was used to analyze SNPs by TaqMan genotyping assays. Disease control rate was evaluated according to RECIST. Adverse effects of sunitinib were registered from medical records. The results of Cox and logistic regression were verified by correction for multiple testing.Kaplan-Meier analysis revealed a reduced progression-free survival in patients with the wild-type (WT) allele of the VEGFA SNP rs699947 compared to variant alleles. Patients with the AA/AC-alleles of the VEGFR1 SNP rs9582036 had an improved median overall survival compared to those with the CC-WT allele what could be confirmed by multivariable Cox proportional hazard regression analyses. No statistically significant associations between the analyzed SNPs and higher risk for adverse effects were observed.The results of this study suggest that most of the selected SNPs in angiogenesis-related genes are not associated with survival of mRCC patients after sunitinib therapy or with adverse effects. Only the VEGFR1 SNP rs9582036 showed a statistically significant association with overall survival. The potential of SNPs as prognostic and predictive markers for sunitinib-treated mRCC patients should be finally assessed by prospective studies.