The Second School of Clinical Medicine, Southern Medical University, Departments of Respiratory and Critical Care Medicine, Guangdong Provincial People's Hospital/Guangdong Academy of Medical Sciences/Guangdong Provincial Geriatrics Institute, Guangzhou, Guangdong, 510080, China.
Departments of Respiratory and Critical Care Medicine, Guangdong Provincial People's Hospital/Guangdong Academy of Medical Sciences/Guangdong Provincial Geriatrics Institute, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510080, China.
Sleep Med. 2020 Jun;70:88-96. doi: 10.1016/j.sleep.2020.02.009. Epub 2020 Feb 24.
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).
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-β 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.
NSCLC patients with OSA showed higher Foxp3Tregs ratio, higher plasma VEGF and TGF-β levels when compared with NSCLC patients without OSA (P < 0.05). In NSCLC patients with OSA or not, subjects with higher Foxp3Treg ratio, higher TGF-β and VEGF levels tended to have poor mean survival time and two-year overall survival (OS, Foxp3Treg: 636.7 vs. 704.8 days, 59.0% vs. 82.6%, P = 0.125; TGF-β: 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).
OSA may up-regulate the expression of circulating TGF-β, VEGF and Foxp3Tregs expression in NSCLC patients. Elevated VEGF level is closely associated with worse short-term survival in NSCLC patients with OSA or not.
确定调节性 T 细胞（Tregs）的抑制功能和血管内皮细胞生长因子（VEGF）水平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。
收集 20 例 OSA 患者、44 例新诊断的 NSCLC 患者（有 OSA 组：n=22，无 OSA 组：n=22）的外周血。采用流式细胞术分析叉头框蛋白 3 加（Foxp3）和 CTLA-4 Tregs 比值。采用酶联免疫吸附试验分析 VEGF、IL-10 和 TGF-β 水平。对有和无 OSA 的 NSCLC 患者进行为期两年的随访。通过受试者工作特征曲线确定最佳截断值。采用 Kaplan-Meier 检验进行生存分析。
与无 OSA 的 NSCLC 患者相比，有 OSA 的 NSCLC 患者的 Foxp3Tregs 比值更高，血浆 VEGF 和 TGF-β 水平也更高（P<0.05）。在有或没有 OSA 的 NSCLC 患者中，Foxp3Treg 比值较高、TGF-β 和 VEGF 水平较高的患者，平均生存时间和两年总生存率（OS）较差（Foxp3Treg：636.7 与 704.8 天，59.0%与 82.6%，P=0.125；TGF-β：637.8 与 698.4 天，57.0%与 84.4%，P=0.054；VEGF：642.9 与 677.5 天，48.6%与 81.3%，P=0.074）。多变量 Cox 回归校正疾病分期和全身治疗后，证实高水平 VEGF 与较差的 OS 相关（HR：1.003；95%CI：1.001-1.005；P=0.021）。
OSA 可能上调 NSCLC 患者循环 TGF-β、VEGF 和 Foxp3Tregs 的表达。在有或没有 OSA 的 NSCLC 患者中，升高的 VEGF 水平与短期生存不良密切相关。
