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循环肿瘤细胞检测在肺部肿瘤诊断中的应用研究

发布时间:2019-05-24 12:27
【摘要】:目的:研究外周血循环肿瘤细胞数目检测与肺癌的临床病理生理特征相关性及在肺癌诊断中的应用价值。方法:2016年5月至2016年11月,在四川省人民医院胸外科共收集89例经胸部CT检查明确有肺部占位病变患者,以及3名健康受试者。术前采集外周血4ml做循环肿瘤细胞计数检测。方法采用叶酸受体免疫磁珠负向筛选+靶向荧光定量PCR法,定义每3ml外周血循环肿瘤细胞数8.7u/3ml的患者为阳性,分析CTC阳性率与年龄、性别、病理类型、临床分期的关系。统计采用SPSS22.0统计软件包进行统计分析,计量资料采用均数±标准差(x±S)的形式表示,对于正态分布资料或者经转化服从正态分布的资料,采用独立样本t检验或者方差分析进行统计分析;对于不服从正态分布的资料,采用秩和检验;计数资料采用频数(%)表示,采用卡方检验进行统计分析;以p0.05为差异有统计学意义。采用Med Calc 11.4.2.0分析软件绘制受试者工作特征性曲线(receiver operating characteristic curve,ROC曲线)来评估循环肿瘤细胞数目检测及临床常用的肿瘤标志物对于肺部肿瘤性质检测的敏感性、特异性,用曲线下面积(area under curve,AUC)来对比循环肿瘤细胞数目检测及肿瘤标记物对于肺部肿瘤的准确性。标志物的最佳Cutoff值根据正确指数(Youden指数)确定。以p0.05为差异有统计学意义。结果:本研究共纳入92例样本,有3名健康受试者,65例术后病理诊断肺癌,肺部良性病变有24例。肺癌患者中CTC计数阳性率明显高于肺部良性病变患者及健康受试者。肺癌CTC平均值为13.61±9.73u/3ml;良性病变CTC平均值为7.90±5.02u/3ml;健康受试者CTC平均值为4.30±1.49u/3ml,差异有统计学意义(p0.001)。肺鳞癌患者CTC数值为14.83±5.83u/3ml,肺腺癌患者CTC数值为12.7±10.68u/3ml,肺鳞癌患者CTC数值高于非腺癌患者,差异有统计学意义(p=0.022)。有淋巴结转移患者CTC数值为14.66±19.06u/3ml;无淋巴结转移肺癌患者CTC数值为12.49±4.06u/3ml,差异有统计学意义(p=0.012)。肿瘤最大直径大于等于7cm患者CTC数值为18.99±4.80u/3ml,大于肿瘤最大直径小于7cm患者,差异有统计学意义(p=0.005)。I-II期肺癌患者CTC数值为11.57±5.38u/3ml;III-IV期患者共计26例,CTC数值为16.66±13.51u/3ml。两者差异有统计学意义(p=0.011)。CTC数值与患者性别、是否吸烟、病理分化程度无关。通过绘制ROC显示循环肿瘤细胞数值检测对肺部肿瘤检测的敏感性(84.6%),特异性(70.8%)。对比CTC与临床常用的肿瘤标志物,结果显示:CTC检测的AUC值为0.804,高于其他肿瘤标志物检测的准确性。结论:免疫磁珠负向筛选+靶向荧光定量PCR法检测CTC对肺癌有良好的诊断能力,检测灵敏度84.6%;CTC数值与肿瘤最大直径、病理类型、淋巴结转移及患者年龄相关;与患者性别、是否吸烟、病理分化程度及肺癌分期无关;与一般肿标志物相比,CTC对肺癌的检测灵敏度更高;但部分研究入组样本较少。
[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 卤standard deviation (x 卤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 卤9.73u 鈮,

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