OBJECTIVE To determine if suppressive function of regulatory T-cells (Tregs) and vascular endothelial cell growth factor (VEGF) levels are closely associated with prognosis of patients with non-small cell lung cancer (NSCLC) and obstructive sleep apnea (OSA). METHODS Peripheral blood from 20 OSA patients, 44 newly diagnosed NSCLC patients with (n = 22) and without (n = 22) OSA was collected. Forkhead box protien 3 plus (Foxp3+) and CTLA-4+ Tregs ratio were analyzed with flow cytometry. Levels of VEGF, IL-10 and TGF-β1 were analyzed with enzyme-linked immuno sorbent assay. NSCLC patients with and without OSA were followed up for two years. Optimal cutoff values were determined by receiver operating characteristic curves. Survival analysis were performed using the Kaplan-Meier test. RESULTS NSCLC patients with OSA showed higher Foxp3+Tregs ratio, higher plasma VEGF and TGF-β1 levels when compared with NSCLC patients without OSA (P < 0.05). In NSCLC patients with OSA or not, subjects with higher Foxp3+Treg ratio, higher TGF-β1 and VEGF levels tended to have poor mean survival time and two-year overall survival (OS, Foxp3+Treg: 636.7 vs. 704.8 days, 59.0% vs. 82.6%, P = 0.125; TGF-β1: 637.8 vs. 698.4 days, 57.0% vs. 84.4%, P = 0.054; VEGF: 642.9 vs. 677.5 days, 48.6% vs. 81.3%, P = 0.074). Multivariate Cox regression adjusted for disease stage and receipt of systemic treatments, confirmed the links between high VEGF level and worse OS (HR: 1.003; 95% CI: 1.001-1.005; P = 0.021). CONCLUSIONS OSA may up-regulate the expression of circulating TGF-β1, VEGF and Foxp3+Tregs expression in NSCLC patients. Elevated VEGF level is closely associated with worse short-term survival in NSCLC patients with OSA or not.

中文翻译：

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非小细胞肺癌和阻塞性睡眠呼吸暂停患者循环调节性T细胞抑制功能和血管内皮生长因子水平的短期预后影响。

目的确定调节性T细胞（Tregs）和血管内皮细胞生长因子（VEGF）水平的抑制功能是否与非小细胞肺癌（NSCLC）和阻塞性睡眠呼吸暂停（OSA）患者的预后密切相关。方法收集20例OSA患者，44例新诊断的NSCLC患者（n = 22）和无（n = 22）OSA的外周血。用流式细胞仪分析了叉头盒蛋白3 plus（Foxp3 +）和CTLA-4 + Tregs的比率。用酶联免疫吸附法分析VEGF，IL-10和TGF-β1的水平。伴有和不伴有OSA的NSCLC患者进行了两年的随访。最佳截止值由接收器工作特性曲线确定。使用Kaplan-Meier检验进行生存分析。结果NSCLC OSA患者显示出较高的Foxp3 + Tregs比，与无OSA的NSCLC患者相比，血浆VEGF和TGF-β1水平更高（P <0.05）。在有或没有OSA的NSCLC患者中，Foxp3 + Treg比率较高，TGF-β1和VEGF水平较高的受试者倾向于平均生存时间和两年总体生存期较差（OS，Foxp3 + Treg：636.7天，相对于704.8天，59.0 ％vs. 82.6％，P = 0.125;TGF-β1：637.8 vs. 698.4天，57.0％vs. 84.4％，P = 0.054; VEGF：642.9 vs. 677.5天，48.6％vs.81.3％，P = 0.074） 。根据疾病阶段和接受全身治疗对多元Cox回归进行了调整，证实了高VEGF水平与OS恶化之间的联系（HR：1.003； 95％CI：1.001-1.005； P = 0.021）。结论OSA可能上调NSCLC患者循环中TGF-β1，VEGF的表达和Foxp3 + Tregs的表达。