Sullivan I, Salazar J, Arqueros C, Andrés M, Sebio A, Majem M, Szafranska J, Martínez E, Páez D, López-Pousa A, Baiget M, Barnadas A
Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
Clin Transl Oncol. 2017 Jul;19(7):884-890. doi: 10.1007/s12094-017-1620-7. Epub 2017 Feb 1.
Several angiogenic prognostic markers are under investigation because of their potential clinical utility, aiming to improve patient outcomes. We hypothesized that genetic variant in the VEGF pathway could be used as prognostic markers of survival in non-small cell lung cancer (NSCLC) patients undergoing pulmonary resection.
We evaluated the relationship between genetic variants in the VEGF pathway and relapse-free survival (RFS, main endpoint) and overall survival (OS, secondary endpoint) among 131 patients with stage I-III NSCLC treated with surgical resection from 2009 to 2013. Clinical, pathological and surgical data were prospectively collected. Twenty-five variants in sixteen relevant genes were selected and genotyped in tumor samples by real time PCR. The Kaplan-Meier method with the log-rank test and Cox's regression models were used for RFS and OS analyses.
With a median follow-up of 36 (min = 2.8; max = 67.4) months, there were 31 (24%) relapses and 31 (24%) deaths. Overall, median RFS was not reached and median OS was 65 [95% confidence interval (CI) 56-75] months. The KRAS rs1137282 and PIK3C2A rs4356203 variants were significantly associated with RFS. For KRAS rs1137282, the 3-year RFS was 76% [95% CI 64-84%] in patients harboring an A/A genotype compared to 53% [95% CI 37-69%] in patients harboring an A/G or G/G genotype (p = 0.02). For PIK3C2A rs4356203, patients with an A/A or an A/G genotype had a 3-year RFS of 72% [95% CI 58-76%], whereas in patients with a G/G genotype was 49% [95% CI 28-70%] (p = 0.02). These associations remained statistically significant after adjusting for all the relevant clinical parameters in the multivariable analysis.
Genetic variants in VEGF pathway may be associated with recurrence in stage I-III NSCLC. Specifically, the KRAS rs1137282 could be considered as a prognostic factor for recurrence in resectable NSCLC patients. Although PIK3C2A rs4356203 was associated with RFS, further analyses are necessary to confirm these data.
由于几种血管生成预后标志物具有潜在的临床应用价值，因此正在对其进行研究，旨在改善患者预后。我们假设血管内皮生长因子（VEGF）通路中的基因变异可作为接受肺切除的非小细胞肺癌（NSCLC）患者生存的预后标志物。
我们评估了2009年至2013年接受手术切除的131例I-III期NSCLC患者中VEGF通路基因变异与无复发生存期（RFS，主要终点）和总生存期（OS，次要终点）之间的关系。前瞻性收集临床、病理和手术数据。选择16个相关基因中的25个变异，并通过实时聚合酶链反应（PCR）对肿瘤样本进行基因分型。采用Kaplan-Meier法结合对数秩检验和Cox回归模型进行RFS和OS分析。
中位随访时间为36（最小值=2.8；最大值=67.4）个月，有31例（24%）复发和31例（24%）死亡。总体而言，未达到中位RFS，中位OS为65[95%置信区间（CI）56-75]个月。KRAS基因rs1137282和PIK3C2A基因rs4356203变异与RFS显著相关。对于KRAS基因rs1137282，携带A/A基因型的患者3年RFS为76%[95%CI 64-84%]，而携带A/G或G/G基因型的患者为53%[95%CI 37-69%]（p=0.02）。对于PIK3C2A基因rs4356203，携带A/A或A/G基因型的患者3年RFS为72%[95%CI 58-76%]，而携带G/G基因型的患者为49%[95%CI 28-70%]（p=0.02）。在多变量分析中对所有相关临床参数进行调整后，这些关联仍具有统计学意义。
VEGF通路中的基因变异可能与I-III期NSCLC的复发有关。具体而言，KRAS基因rs1137282可被视为可切除NSCLC患者复发的预后因素。虽然PIK3C2A基因rs4356203与RFS相关，但需要进一步分析来证实这些数据。
