Oncology Department, Beijing Chest Hospital of Capital Medical University, Beijing, China.
Laboratory of Molecular Biology, Beijing Chest Hospital of Capital Medical University, Beijing, China.
Genet Test Mol Biomarkers. 2020 Dec;24(12):798-803. doi: 10.1089/gtmb.2020.0173.
Hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) are key angiogenic regulatory factors. The aim of this study was to identify the most useful prognostic angiogenic factors in advanced nonsmall cell lung cancer (NSCLC) without known driver gene mutations. Eligible patients were pathologically confirmed to have advanced NSCLC without known driver mutations. All patients were treated with standard first-line chemotherapy ± bevacizumab. Serum concentrations of HIF-1α, VEGF, sVEGFR1, sVEGFR2, and endostatin were measured via enzyme-linked immunosorbent assays (ELISAs) prior to and after two cycles of treatment. Area under the curve (AUC) and optimal cutoff values were calculated by receiver operator characteristic curve (ROC) analyses. The parameters that predicted survival were evaluated by univariate and multivariate Cox proportional hazard analyses. A total of 47 patients were included in this study. HIF-1α levels decreased significantly after treatment in the nonprogressing (partial response/stable disease) patient group (707.94 vs. 355.53 pg/mL, = 0.002), but increased levels were seen in patients with progressive disease, however, the extent of change did not reach significance (173.70 vs. 416.34 pg/mL, = 0.078). An HIF-1α ratio of 1.18 was chosen as the best point to predict treatment response through ROC analyses. Via univariate and multivariate analyses, we found that patients with a HIF-1α ratio ≥1.18 after treatment were significantly more likely to have a prolonged progression-free survival (PFS, HR 0.303, 95% CI: 0.153-0.603, = 0.001) and overall survival (OS, HR 0.436, 95% CI: 0.153-0.603, = 0.025). We identified the pretreatment to posttreatment HIF-1α ratio as a promising predictor for PFS and OS in NSCLC patients without known driver mutations.
缺氧诱导因子-1α（HIF-1α）和血管内皮生长因子（VEGF）是关键的血管生成调节因子。本研究旨在确定无已知驱动基因突变的晚期非小细胞肺癌（NSCLC）中最有用的预后血管生成因子。符合条件的患者经病理证实患有晚期 NSCLC 且无已知驱动突变。所有患者均接受标准一线化疗±贝伐珠单抗治疗。在治疗前和治疗后两个周期通过酶联免疫吸附试验（ELISA）测量血清中 HIF-1α、VEGF、sVEGFR1、sVEGFR2 和内皮抑素的浓度。通过接收者操作特征曲线（ROC）分析计算曲线下面积（AUC）和最佳截断值。通过单变量和多变量 Cox 比例风险分析评估预测生存的参数。本研究共纳入 47 例患者。在非进展（部分缓解/疾病稳定）患者组中，治疗后 HIF-1α水平显著降低（707.94 与 355.53 pg/mL， = 0.002），但在疾病进展患者中，HIF-1α水平升高，但变化幅度无统计学意义（173.70 与 416.34 pg/mL， = 0.078）。通过 ROC 分析，选择 HIF-1α 比值 1.18 作为预测治疗反应的最佳切点。通过单变量和多变量分析，我们发现治疗后 HIF-1α 比值≥1.18 的患者无进展生存期（PFS，HR 0.303，95%CI：0.153-0.603， = 0.001）和总生存期（OS，HR 0.436，95%CI：0.153-0.603， = 0.025）显著延长的可能性更大。我们发现，治疗前到治疗后的 HIF-1α 比值是无已知驱动基因突变的 NSCLC 患者 PFS 和 OS 的一个很有前途的预测指标。
