非小细胞肺癌血浆天然CD25抗体及FOXP3抗体的表达变化及其作为诊断标志物的探讨  

Expression of natural antibody against CD25 and FOXP3 in plasma of nonsmall cell lung cancer and their diagnostic value as biomarkers

作　　者：赵欢 张萱[2] 李庆海(指导) ZHAO Huan;ZHANG Xuan;LI Qinghai(Department of Endocrinology,Qingdao Municipal Hospital,Qingdao University,Qingdao 266071,China)

机构地区：[1]青岛大学附属青岛市市立医院内分泌科,青岛266071 [2]吉林大学第二医院吉林省分子与遗传学重点实验室,长春130031 [3]青岛大学附属青岛市市立医院呼吸科,青岛266071

出　　处：《中国免疫学杂志》2022年第1期80-85,共6页Chinese Journal of Immunology

摘　　要：目的:探讨天然CD25和FOXP3抗体在非小细胞肺癌(NSCLC)患者血浆表达变化的临床意义及其作为诊断标志物的潜能。方法:选取青岛大学附属青岛市立医院胸外科首次确诊且未经任何治疗的NSCLC患者200例及同期性别、年龄、吸烟史相匹配的健康志愿者190例,收集两组血液样本。基于CD25及FOXP3分子结构,利用表位预测软件(http://www.iedb.org)设计并合成3条线性抗原肽(即CD25a、CD25b、FOXP3)并外送化工公司合成,通过自行建立的优化ELISA检测方法,检测NSCLC患者及健康对照组血浆CD25及FOXP3抗体的表达水平,并分析CD25及FOXP3抗体的表达与临床病理特征之间的关系。同时绘制ROC曲线,评估CD25及FOXP3抗体对不同TNM分期NSCLC的诊断价值。结果:NSCLCⅡ~Ⅳ期患者血浆CD25a、FOXP3抗体的表达较健康对照组显著增加(0.66±0.18 vs 0.52±0.17,P<0.001;0.60±0.23 vs 0.53±0.25,P<0.001),NSCLC患者血浆CD25b抗体的表达较健康对照显著降低,这一变化在Ⅰ~Ⅱ期患者中尤为显著(0.37±0.21 vs 0.43±0.22,P<0.001)。NSCLC患者血浆CD25a抗体的表达与性别、病理类型、淋巴结转移有关(P均<0.05),与年龄、肿瘤分化程度、肿瘤大小、TNM分期、吸烟史无关(P均>0.05)。CD25b抗体的表达与性别、年龄、肿瘤分化程度有关(P均<0.05),与病理类型、淋巴结转移、肿瘤大小、TNM分期、吸烟史无关(P均>0.05),而FOXP3抗体的表达仅与肿瘤分化程度有关(P<0.05)。对CD25、FOXP3抗体诊断NSCLC的效能评估,CD25a曲线下面积为0.727(95%CI:0.677~0.778),最佳截断值为0.55,敏感度为77%,特异度为64%;CD25b曲线下面积为0.601(95%CI:0.545~0.657),最佳截断值为0.35,敏感度为62%,特异度为57%;FOXP3曲线下面积为0.613(95%CI:0.557~0.669),最佳截断值为0.54,敏感度为58%,特异度为65%。结论:检测CD25a天然抗体可辅助NSCLC的早期诊断;血浆CD25b天然抗体在早期NSCLC(Ⅰ+Ⅱ期)表达降低,对预测早期NSCLC有一定价值。Objective:To investigate the expression and clinical significance of natural antibodies against CD25 and FOXP3 in the plasma of patients with non-small cell lung cancer(NSCLC).Methods:Blood samples were collected from 200 NSCLC patients who were first diagnosed with NSCLC and did not receive any anti-cancer treatment at the Department of Thoracic Surgery,Qingdao Municipal Hospital,Qingdao University and 190 healthy volunteers whose gender,age and smoking history were well match with NSCLC patients. Based on the molecular structure of CD25 and FOXP3,three linear peptide antigens derived from CD25 and FOXP3 protein,namely CD25 a,CD25 b,FOXP3 were designed using computational epitope prediction software(http://www.iedb.org)and synthesized by solid-phase chemistry. The optimized ELISA test was established to detect CD25 and FOXP3 antibodies in the plasma of NSCLC patients and healthy controls. The relationship between the expression levels of CD25 and FOXP3 antibodies and clinicopathological characteristics were analyzed. ROC curves were also drawn to evaluate the diagnostic value of CD25 and FOXP3 antibodies for NSCLC with different TNM stages.Results:The expression of CD25 a and FOXP3 antibodies in NSCLC patients,especially stage Ⅱ~Ⅳ patients,was significantly increased compared with healthy controls(0.66±0.18 vs 0.52±0.17,P<0.001;0.60±0.23 vs0.53±0.25,P<0.001). The expression of CD25 b antibody in the plasma of NSCLC patients was significantly lower than that of healthy controls. This change was particularly significant in patients with stage Ⅰ~Ⅱ(0.37±0.21 vs 0.43±0.22,P<0.001). The expression of CD25 a antibody in NSCLC patients was correlated with gender,pathological type,and lymph node metastasis(all P<0.05),and it was not correlated with age,tumor differentiation,tumor size,TNM stage and smoking history(all P>0.05). The expression of CD25 b antibody was correlated with gender,age and tumor differentiation(all P<0.05),and it was not correlated with pathological type,lymph node metastasis,tumor siz

关 键 词：天然抗体 CD25 FOXP3 非小细胞肺癌 

分 类 号：R563.9[医药卫生—呼吸系统]