發(fā)布時(shí)間：2018-04-19 02:30

  本文選題：內(nèi)皮細(xì)胞特異性因子-1 + 非小細(xì)胞肺癌　； 參考：《南京醫(yī)科大學(xué)》2017年博士論文

【摘要】：背景和目的原發(fā)性支氣管肺癌(簡(jiǎn)稱肺癌)是全球范圍內(nèi)發(fā)病率和死亡率居首位的惡性腫瘤,其中非小細(xì)胞肺癌(NSCLC)占85%。惡性胸腔積液(MPE)是晚期NSCLC患者的常見(jiàn)并發(fā)癥,約有50%的晚期NSCLC患者出現(xiàn)MPE。然而MPE尚無(wú)敏感性和特異性均令人滿意的生物標(biāo)志物。尋找新的MPE診斷及預(yù)后標(biāo)志物,對(duì)于MPE的診斷和預(yù)后判斷有著重要的意義。本文擬通過(guò)檢測(cè)胸腔積液中內(nèi)皮細(xì)胞特異性因子-1(ESM-1)的水平,探索ESM-1在MPE中的表達(dá)特征及其臨床意義,通過(guò)ROC曲線及生存分析,評(píng)價(jià)ESM-1對(duì)NSCLC相關(guān)性MPE的診斷及預(yù)后判斷價(jià)值。資料和方法收集2011年7月至2013年4月于南京市胸科醫(yī)院呼吸科住院的NSCLC相關(guān)性MPE患者70例(研究組),同時(shí)將年齡、性別相匹配的50例良性胸腔積液患者作為對(duì)照組。采用ELISA試劑盒檢測(cè)兩組患者胸腔積液中ESM-1的水平,化學(xué)發(fā)光法試劑盒檢測(cè)胸腔積液中的CEA水平。通過(guò)ROC曲線分析不同診斷界值時(shí),胸腔積液ESM-1和CEA診斷NSCLC相關(guān)性MPE的敏感性和特異性。ESM-1和CEA聯(lián)合檢測(cè)時(shí),先用logistic回歸進(jìn)行分析,做出概率預(yù)測(cè)值,并以此值繪制ROC曲線,并計(jì)算出二者聯(lián)合診斷的效能。對(duì)研究組進(jìn)行隨訪,同時(shí)根據(jù)ESM-1水平高低將研究組分為ESM-1高水平和低水平兩個(gè)亞組。用Kaplan-Meier法計(jì)算生存曲線,單因素和多因素分析MPE中ESM-1的水平高低對(duì)總生存期(OS)的影響。結(jié)果(1)兩組患者在年齡、性別等方面差異無(wú)統(tǒng)計(jì)學(xué)意義。研究組中ESM-1及CEA水平均高于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(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)通過(guò)ROC曲線分析不同診斷界值時(shí),分析胸腔積液ESM-1和CEA診斷MPE的敏感性和特異性。ESM-1和CEA的ROC曲線下面積分別為0.884和0.863。ESM-1 95%的可信區(qū)間為0.825-0.943,當(dāng)最佳截?cái)嘀等?9.58ng/ml時(shí),ESM-1診斷MPE的靈敏度、特異度和準(zhǔn)確性分別為81.4%、84.0%和82.5%。CEA 95%的可信區(qū)間為0.798-0.929,當(dāng)最佳截?cái)嘀等?.52ng/ml時(shí),CEA診斷MPE的靈敏度、特異度和準(zhǔn)確度分別為68.6%、96.0%和80.0%。(3)ESM-1和CEA聯(lián)合診斷NSCLC相關(guān)性MPE的靈敏度、特異性和準(zhǔn)確性較單一檢測(cè)ESM-1均有所增高(85.7%,96.0%,82.7%)。(4)Kaplan-Meier生存曲線發(fā)現(xiàn),NSCLC相關(guān)性MPE中,相對(duì)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)。單因素和多因素生存分析提示ESM-1可能作為NSCLC相關(guān)性MPE的獨(dú)立預(yù)后預(yù)測(cè)因子。結(jié)論(1)ESM-1水平在NSCLC相關(guān)性MPE中顯著增高,可以作為生物標(biāo)志物用于良惡性胸腔積液的鑒別診斷。與CEA聯(lián)合檢測(cè)可進(jìn)一步提高診斷效能;(2)胸腔積液ESM-1可能作為NSCLC相關(guān)性MPE患者預(yù)后的獨(dú)立預(yù)測(cè)因子。MPE中ESM-1水平越高,提示NSCLC相關(guān)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 鹵4.51ng/ml vs.13.67 鹵0.92 ng / ml vs.13.67 鹵0.92 ng / ml 鹵0.001ng / ml CEA: 185.26 鹵29.20ng/ml vs.4.02 鹵0.37ng vs.4.02 鹵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.
【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：R734.2

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本文編號(hào)：1771196