Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Sant Quintí, 89, 08041, Barcelona, Spain.
Genetics Department, Hospital de la Santa Creu i Sant Pau, Sant Quintí, 89, 08041, Barcelona, Spain.
Angiogenesis. 2019 Aug;22(3):433-440. doi: 10.1007/s10456-019-09668-y. Epub 2019 Apr 11.
Clinical and pathological characteristics are still considered prognostic markers in metastatic non-small-cell lung cancer (NSCLC) patients but they cannot explain all interindividual variability. Tumoral angiogenesis mediated by the vascular endothelial growth factor (VEGF) is critical for the progression and metastasis of the disease. We aimed to investigate the prognostic role of genetic variants within the VEGF pathway in patients with metastatic NSCLC.
We prospectively included 170 patients with metastatic NSCLC treated with first-line platinum-based chemotherapy. A comprehensive panel of single-nucleotide polymorphisms (SNPs) in genes belonging to the VEGF pathway (VEGFA, VEGFR1/FLT1, VEGFR2/KDR, GRB2, ITGAV, KISS1, KRAS, PRKCE, HIF1α, MAP2K4, MAP2K6, and MAPK11) were genotyped in blood DNA samples. SNPs were evaluated for association with overall survival (OS) and progression-free survival (PFS).
In multivariate analyses adjusted for patient characteristics, we found that VEGFA rs2010963 and VEGFR2 rs2071559 were significantly associated with OS [Hazard Ratio (HR) 0.7 (0.5-0.9); p = 0.026 and HR 1.5 (1.1-2.3); p = 0.025, respectively]. Additionally, ITGAV rs35251833 and MAPK11 rs2076139 were significantly associated with PFS [HR 2.5 (1.4-4.3; p = 0.002 and HR 0.6 (0.5-0.9); p = 0.013, respectively].
Our findings reinforce the potential clinical value of germline variants in VEGFA and VEGFR2 and show for the first time variants in ITGAV and MAPK11 as promising prognostic markers in metastatic NSCLC patients receiving platinum-based chemotherapy.
临床和病理特征仍被认为是转移性非小细胞肺癌（NSCLC）患者的预后标志物，但它们无法解释所有个体间的差异。血管内皮生长因子（VEGF）介导的肿瘤血管生成对于疾病的进展和转移至关重要。我们旨在研究 VEGF 通路中遗传变异在转移性 NSCLC 患者中的预后作用。
我们前瞻性纳入了 170 名接受一线铂类化疗治疗的转移性 NSCLC 患者。对属于 VEGF 通路（VEGFA、VEGFR1/FLT1、VEGFR2/KDR、GRB2、ITGAV、KISS1、KRAS、PRKCE、HIF1α、MAP2K4、MAP2K6 和 MAPK11）的基因中的单核苷酸多态性（SNP）进行了全面分析。在血液 DNA 样本中对 SNP 进行了基因分型。评估了 SNP 与总生存期（OS）和无进展生存期（PFS）的相关性。
在调整患者特征的多变量分析中，我们发现 VEGFA rs2010963 和 VEGFR2 rs2071559 与 OS 显著相关[风险比（HR）0.7（0.5-0.9）；p=0.026 和 HR 1.5（1.1-2.3）；p=0.025]。此外，ITGAV rs35251833 和 MAPK11 rs2076139 与 PFS 显著相关[HR 2.5（1.4-4.3；p=0.002 和 HR 0.6（0.5-0.9）；p=0.013]。
我们的研究结果强化了 VEGF 和 VEGFR2 中种系变异的潜在临床价值，并首次显示 ITGAV 和 MAPK11 中的变异是接受铂类化疗的转移性 NSCLC 患者有希望的预后标志物。
