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循環(huán)腫瘤細(xì)胞檢測在肺部腫瘤診斷中的應(yīng)用研究

發(fā)布時(shí)間:2019-05-24 12:27
【摘要】:目的:研究外周血循環(huán)腫瘤細(xì)胞數(shù)目檢測與肺癌的臨床病理生理特征相關(guān)性及在肺癌診斷中的應(yīng)用價(jià)值。方法:2016年5月至2016年11月,在四川省人民醫(yī)院胸外科共收集89例經(jīng)胸部CT檢查明確有肺部占位病變患者,以及3名健康受試者。術(shù)前采集外周血4ml做循環(huán)腫瘤細(xì)胞計(jì)數(shù)檢測。方法采用葉酸受體免疫磁珠負(fù)向篩選+靶向熒光定量PCR法,定義每3ml外周血循環(huán)腫瘤細(xì)胞數(shù)8.7u/3ml的患者為陽性,分析CTC陽性率與年齡、性別、病理類型、臨床分期的關(guān)系。統(tǒng)計(jì)采用SPSS22.0統(tǒng)計(jì)軟件包進(jìn)行統(tǒng)計(jì)分析,計(jì)量資料采用均數(shù)±標(biāo)準(zhǔn)差(x±S)的形式表示,對于正態(tài)分布資料或者經(jīng)轉(zhuǎn)化服從正態(tài)分布的資料,采用獨(dú)立樣本t檢驗(yàn)或者方差分析進(jìn)行統(tǒng)計(jì)分析;對于不服從正態(tài)分布的資料,采用秩和檢驗(yàn);計(jì)數(shù)資料采用頻數(shù)(%)表示,采用卡方檢驗(yàn)進(jìn)行統(tǒng)計(jì)分析;以p0.05為差異有統(tǒng)計(jì)學(xué)意義。采用Med Calc 11.4.2.0分析軟件繪制受試者工作特征性曲線(receiver operating characteristic curve,ROC曲線)來評估循環(huán)腫瘤細(xì)胞數(shù)目檢測及臨床常用的腫瘤標(biāo)志物對于肺部腫瘤性質(zhì)檢測的敏感性、特異性,用曲線下面積(area under curve,AUC)來對比循環(huán)腫瘤細(xì)胞數(shù)目檢測及腫瘤標(biāo)記物對于肺部腫瘤的準(zhǔn)確性。標(biāo)志物的最佳Cutoff值根據(jù)正確指數(shù)(Youden指數(shù))確定。以p0.05為差異有統(tǒng)計(jì)學(xué)意義。結(jié)果:本研究共納入92例樣本,有3名健康受試者,65例術(shù)后病理診斷肺癌,肺部良性病變有24例。肺癌患者中CTC計(jì)數(shù)陽性率明顯高于肺部良性病變患者及健康受試者。肺癌CTC平均值為13.61±9.73u/3ml;良性病變CTC平均值為7.90±5.02u/3ml;健康受試者CTC平均值為4.30±1.49u/3ml,差異有統(tǒng)計(jì)學(xué)意義(p0.001)。肺鱗癌患者CTC數(shù)值為14.83±5.83u/3ml,肺腺癌患者CTC數(shù)值為12.7±10.68u/3ml,肺鱗癌患者CTC數(shù)值高于非腺癌患者,差異有統(tǒng)計(jì)學(xué)意義(p=0.022)。有淋巴結(jié)轉(zhuǎn)移患者CTC數(shù)值為14.66±19.06u/3ml;無淋巴結(jié)轉(zhuǎn)移肺癌患者CTC數(shù)值為12.49±4.06u/3ml,差異有統(tǒng)計(jì)學(xué)意義(p=0.012)。腫瘤最大直徑大于等于7cm患者CTC數(shù)值為18.99±4.80u/3ml,大于腫瘤最大直徑小于7cm患者,差異有統(tǒng)計(jì)學(xué)意義(p=0.005)。I-II期肺癌患者CTC數(shù)值為11.57±5.38u/3ml;III-IV期患者共計(jì)26例,CTC數(shù)值為16.66±13.51u/3ml。兩者差異有統(tǒng)計(jì)學(xué)意義(p=0.011)。CTC數(shù)值與患者性別、是否吸煙、病理分化程度無關(guān)。通過繪制ROC顯示循環(huán)腫瘤細(xì)胞數(shù)值檢測對肺部腫瘤檢測的敏感性(84.6%),特異性(70.8%)。對比CTC與臨床常用的腫瘤標(biāo)志物,結(jié)果顯示:CTC檢測的AUC值為0.804,高于其他腫瘤標(biāo)志物檢測的準(zhǔn)確性。結(jié)論:免疫磁珠負(fù)向篩選+靶向熒光定量PCR法檢測CTC對肺癌有良好的診斷能力,檢測靈敏度84.6%;CTC數(shù)值與腫瘤最大直徑、病理類型、淋巴結(jié)轉(zhuǎn)移及患者年齡相關(guān);與患者性別、是否吸煙、病理分化程度及肺癌分期無關(guān);與一般腫標(biāo)志物相比,CTC對肺癌的檢測靈敏度更高;但部分研究入組樣本較少。
[Abstract]:Objective: to study the correlation between the number of circulating tumor cells in peripheral blood and the clinicopathological characteristics of lung cancer and its application value in the diagnosis of lung cancer. Methods: from May 2016 to November 2016, 89 patients with pulmonary space occupying lesions and 3 healthy subjects were collected from chest surgery Department of Sichuan people's Hospital. Peripheral blood 4ml was collected before operation for detection of circulating tumor cell count. Methods folic acid receptor immunomagnetizing beads were used to screen targeted fluorescence quantitative PCR. The number of 8.7u/3ml cells in peripheral blood circulation per 3ml was defined as positive. The positive rate of CTC and age, sex and pathological type were analyzed. The relationship between clinical stage and clinical stage. The statistical analysis is carried out by SPSS22.0 statistical software package, and the measurement data are expressed in the form of mean 鹵standard deviation (x 鹵S). For the normal distribution data or the transformed data obeying the normal distribution, Independent sample t test or variance analysis were used for statistical analysis. For the data that do not obey the normal distribution, the rank sum test is used, the counting data is expressed by frequency (%), and the chi-square test is used for statistical analysis, and the difference between p0.05 and p0.05 is statistically significant. Med Calc 11.4.2.0 analysis software was used to draw the (receiver operating characteristic curve,ROC curve of the working characteristic curve of the subjects to evaluate the sensitivity of circulating tumor cells and clinical tumor markers to the detection of lung tumor properties. Specific, using the area under the curve (area under curve,AUC) to compare the number of circulating tumor cells and the accuracy of tumor markers for lung tumors. The best cuff value of the marker was determined according to the correct index (Youden index). The difference between p0.05 and p0.05 was statistically significant. Results: a total of 92 samples were included in this study, including 3 healthy subjects, 65 cases of lung cancer diagnosed pathologically and 24 cases of benign pulmonary lesions. The positive rate of CTC count in patients with lung cancer was significantly higher than that in patients with benign pulmonary lesions and healthy subjects. The average CTC of lung cancer was 13.61 鹵9.73u 鈮,

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