内皮细胞特异性因子-1在非小细胞肺癌相关性恶性胸腔积液中的临床意义

发布时间：2018-04-19 02:30

本文选题：内皮细胞特异性因子-1 + 非小细胞肺癌　；参考：《南京医科大学》2017年博士论文

【摘要】：背景和目的原发性支气管肺癌(简称肺癌)是全球范围内发病率和死亡率居首位的恶性肿瘤,其中非小细胞肺癌(NSCLC)占85%。恶性胸腔积液(MPE)是晚期NSCLC患者的常见并发症,约有50%的晚期NSCLC患者出现MPE。然而MPE尚无敏感性和特异性均令人满意的生物标志物。寻找新的MPE诊断及预后标志物,对于MPE的诊断和预后判断有着重要的意义。本文拟通过检测胸腔积液中内皮细胞特异性因子-1(ESM-1)的水平,探索ESM-1在MPE中的表达特征及其临床意义,通过ROC曲线及生存分析,评价ESM-1对NSCLC相关性MPE的诊断及预后判断价值。资料和方法收集2011年7月至2013年4月于南京市胸科医院呼吸科住院的NSCLC相关性MPE患者70例(研究组),同时将年龄、性别相匹配的50例良性胸腔积液患者作为对照组。采用ELISA试剂盒检测两组患者胸腔积液中ESM-1的水平,化学发光法试剂盒检测胸腔积液中的CEA水平。通过ROC曲线分析不同诊断界值时,胸腔积液ESM-1和CEA诊断NSCLC相关性MPE的敏感性和特异性。ESM-1和CEA联合检测时,先用logistic回归进行分析,做出概率预测值,并以此值绘制ROC曲线,并计算出二者联合诊断的效能。对研究组进行随访,同时根据ESM-1水平高低将研究组分为ESM-1高水平和低水平两个亚组。用Kaplan-Meier法计算生存曲线,单因素和多因素分析MPE中ESM-1的水平高低对总生存期(OS)的影响。结果(1)两组患者在年龄、性别等方面差异无统计学意义。研究组中ESM-1及CEA水平均高于对照组,差异有统计学意义(ESM-1:51.17 ± 4.51ng/ml vs.13.67 ± 0.92ng/ml,p0.001;CEA:185.26 ± 29.20ng/ml vs.4.02 ± 0.37ng/ml,p0.001)。(2)通过ROC曲线分析不同诊断界值时,分析胸腔积液ESM-1和CEA诊断MPE的敏感性和特异性。ESM-1和CEA的ROC曲线下面积分别为0.884和0.863。ESM-1 95%的可信区间为0.825-0.943,当最佳截断值取19.58ng/ml时,ESM-1诊断MPE的灵敏度、特异度和准确性分别为81.4%、84.0%和82.5%。CEA 95%的可信区间为0.798-0.929,当最佳截断值取8.52ng/ml时,CEA诊断MPE的灵敏度、特异度和准确度分别为68.6%、96.0%和80.0%。(3)ESM-1和CEA联合诊断NSCLC相关性MPE的灵敏度、特异性和准确性较单一检测ESM-1均有所增高(85.7%,96.0%,82.7%)。(4)Kaplan-Meier生存曲线发现,NSCLC相关性MPE中,相对于ESM-1低水平患者而言,ESM-1水平增高者(19.58ng/ml)生存期短(22.09月vs.11.49月,p=0.003)。单因素和多因素生存分析提示ESM-1可能作为NSCLC相关性MPE的独立预后预测因子。结论(1)ESM-1水平在NSCLC相关性MPE中显著增高,可以作为生物标志物用于良恶性胸腔积液的鉴别诊断。与CEA联合检测可进一步提高诊断效能;(2)胸腔积液ESM-1可能作为NSCLC相关性MPE患者预后的独立预测因子。MPE中ESM-1水平越高,提示NSCLC相关性MPE患者OS越短。
[Abstract]:Background and objective Primary bronchial lung cancer (lung cancer) is one of the leading malignant tumors in the world, with NSCLC accounting for 85%.Malign pleural effusion (MPE) is a common complication in advanced NSCLC patients, about 50% of advanced NSCLC patients have MPEs.However, there is no biomarker with satisfactory sensitivity and specificity for MPE.Finding new MPE diagnosis and prognostic markers is of great significance for the diagnosis and prognosis of MPE.The expression of ESM-1 in MPE and its clinical significance were studied by detecting the level of ECF-ESM-1 in pleural effusion. The ROC curve and survival analysis were used to evaluate the value of ESM-1 in the diagnosis and prognosis of NSCLC related MPE.Materials and methods from July 2011 to April 2013, 70 patients with NSCLC associated MPE (study group) and 50 patients with benign pleural effusion matched with age and sex were collected from respiratory department of Nanjing chest Hospital as control group.The levels of ESM-1 in pleural effusion and CEA in pleural effusion were detected by ELISA kit and chemiluminescence kit respectively.When different diagnostic thresholds were analyzed by ROC curve, the sensitivity and specificity of pleural effusion ESM-1 and CEA in the diagnosis of NSCLC related MPE were detected. ESM-1 and CEA were analyzed by logistic regression, and the probability predictive value was obtained, and the ROC curve was drawn.The effectiveness of the combined diagnosis was calculated.According to the level of ESM-1, the study group was divided into two subgroups: high level and low level of ESM-1.The survival curve was calculated by Kaplan-Meier method. The influence of ESM-1 level in MPE on total survival time was analyzed by single factor and multivariate analysis.Results (1) there was no significant difference in age and sex between the two groups.The levels of ESM-1 and CEA in the study group were significantly higher than those in the control group. The difference was statistically significant (ESM-1: 51.17 卤4.51ng/ml vs.13.67 卤0.92 ng / ml vs.13.67 卤0.92 ng / ml 卤0.001ng / ml CEA: 185.26 卤29.20ng/ml vs.4.02 卤0.37ng vs.4.02 卤0.37ngml / ml = 0.001ng / min).Sensitivity and specificity of ESM-1 and CEA in the diagnosis of MPE in pleural effusion. The area under ROC curve of ESM-1 and CEA was 0.884 and 0.863.ESM-1 95% confidence interval was 0.825-0.943, respectively. When the best truncation value was 19.58ng/ml, the sensitivity of ESM-1 in the diagnosis of MPE was obtained.The confidence intervals of 81.4% and 95% of 82.5%.CEA were 0.798-0.929, respectively. The sensitivity, specificity and accuracy of MPE were 68.6% and 96.0%, respectively, and the sensitivity of 80.0%.(3)ESM-1 and CEA in the diagnosis of NSCLC related MPE were 68.6% and 96.0%, respectively.The specificity and accuracy of ESM-1 were higher than that of single ESM-1 detection. The survival time was shorter (P 0.003) in the patients with higher ESM-1 level than in the patients with lower ESM-1 level (P 0.003), and 82.7% and 82.7% Kaplan-Meier survival curve were higher than that in the patients with lower ESM-1 level.Univariate and multivariate survival analysis suggested that ESM-1 might be an independent prognostic predictor of NSCLC related MPE.Conclusion the level of ESM-1 in NSCLC associated MPE is significantly higher than that in control group. It can be used as a biomarker for differential diagnosis of benign and malignant pleural effusion.Combined detection with CEA can further improve the diagnostic efficacy. ESM-1 in pleural effusion may be an independent predictor of prognosis in patients with MPE associated with NSCLC. The higher the level of ESM-1 in MPE, the shorter the OS in NSCLC associated MPE patients.
【学位授予单位】：南京医科大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R734.2

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