Medical Research Center of Guangdong General Hospital, Guangdong Lung Cancer Institute, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, Peoples Republic of China.
Med Oncol. 2012 Jun;29(2):627-32. doi: 10.1007/s12032-011-9924-x. Epub 2011 Apr 3.
We sought to find blood-based biomarkers that can be used to predict efficacy in advanced non-small cell lung cancer patients treated with bevacizumab plus chemotherapy. Blood was collected before treatment and after 6 weeks of therapy from patients who were participating in a phase 4 trial. Plasma vascular endothelial growth factor (VEGF) levels were evaluated by ELISA. A total of eight single nucleotide polymorphisms in four candidate genes were analyzed by PCR and sequencing. A total of 45 patients enrolled in a clinical trial at Guangdong General Hospital between August 2007 and March 2008 were used as subjects. The median survival times of OS was 25.6 and 13.4 months in the low and high groups, respectively, when the median posttreatment plasma VEGF level (46.63 pg/ml) was used as the cut-off point (P = 0.0284). Patients carrying the AA genotype at the -6C > A polymorphism in laminin 5 (LN5) were more likely to exhibit reduced hemoglobin compared with patients carrying the CA/CC genotype (OR = 8.364, χ(2) = 5.34, P = 0.021). Similar associations were found at the -89A > G and -260C > A polymorphisms in LN5. Patients with the CC genotype at the -6C > A polymorphism in LN5 had an increased risk of neutropenia than those with the CA/AA genotype (OR = 4.444, χ(2) = 5.116, P = 0.030). Our results show improved survival in patients with lower posttreatment plasma VEGF levels treated with bevacizumab plus chemotherapy; thus, the posttreatment plasma VEGF level may be a promising biomarker to predict clinical benefit early in the course of therapy. Polymorphisms in LN5 were associated with a reduced level of hemoglobin and neutropenia.
我们试图寻找可用于预测接受贝伐单抗联合化疗的晚期非小细胞肺癌患者疗效的血液生物标志物。从参加 4 期临床试验的患者中采集治疗前和治疗 6 周后的血液。通过 ELISA 评估血浆血管内皮生长因子 (VEGF) 水平。通过 PCR 和测序分析了四个候选基因中的 8 个单核苷酸多态性。2007 年 8 月至 2008 年 3 月，广东总医院的一项临床试验共纳入 45 例患者作为研究对象。当以治疗后中位血浆 VEGF 水平（46.63pg/ml）作为截止点时，OS 的中位生存时间分别为低组和高组的 25.6 和 13.4 个月（P = 0.0284）。与携带 CA/CC 基因型的患者相比，携带层粘连蛋白 5（LN5）-6C＞A 多态性 AA 基因型的患者更有可能出现血红蛋白降低（OR = 8.364，X² = 5.34，P = 0.021）。在 LN5 的-89A＞G 和-260C＞A 多态性中也发现了类似的关联。与 CA/AA 基因型相比，携带 LN5-6C＞A 多态性 CC 基因型的患者发生中性粒细胞减少症的风险增加（OR = 4.444，X² = 5.116，P = 0.030）。我们的结果表明，贝伐单抗联合化疗后血浆 VEGF 水平较低的患者生存时间改善；因此，治疗后血浆 VEGF 水平可能是预测治疗早期临床获益的有前途的生物标志物。LN5 中的多态性与血红蛋白和中性粒细胞减少症的降低水平有关。
