临床Ⅰ期非小细胞肺癌诊断模型构建:基于临床影像学特征联合叶酸受体阳性循环肿瘤细胞检测的研究

Establishment of a diagnostic model for clinical stage Ⅰ non-small cell lung cancer: A study based on clinical imaging features combined with folate receptor-positive circulating tumor cells tests

目的分析叶酸受体阳性循环肿瘤细胞(folate receptor-positive circulating tumor cells,FR^(+)CTC)与患者肺部病灶良恶性的相关性,建立基于临床资料、影像学和FR^(+)CTC的肺部肿物恶性预测模型。方法回顾性分析青岛大学附属医院2018年9月至2019年12月1 277例行外周血循环肿瘤细胞检查且病理结果明确的肺结节及肺肿瘤患者的临床资料,其中男518例、女759例,中位年龄为57(29~85)岁。随机将患者分配到试验组和验证组,进行单因素及多因素分析,建立Nomogram预测模型,对其进行内部及外部验证,受试者工作特征(ROC)曲线检验模型区分度,校准曲线检验模型一致性。结果试验组非小细胞肺癌患者925例、良性疾病患者113例;验证组非小细胞肺癌患者219例、良性疾病患者20例,非小细胞肺癌患者外周血中FR^(+)CTC明显高于肺部良性疾病患者(P<0.001)。多因素分析显示年龄≥60岁、女性、FR^(+)CTC值>8.7 FU/3 m L、胸膜牵拉征阳性、结节直径、毛刺征阳性、结节中实性成分直径比值<1是病灶直径≤4 cm肺肿物良恶性病变的独立危险因素。建立Nomogram预测模型,区分度检验试验组ROC曲线下面积(AUC)值为0.918,敏感性为86.36%,特异性为83.19%;验证组AUC值为0.903,模型敏感性为79.45%,特异性为90.00%,表明Nomogram模型区分度良好。校准曲线表明Nomogram预测模型一致性良好。结论非小细胞肺癌患者外周血中FR^(+)CTC显著高于肺部良性疾病患者。本研究建立的临床Ⅰ期非小细胞肺癌诊断模型精准度良好,可以为临床诊断提供依据。

Objective To analyze the correlation between folate receptor-positive circulating tumor cells(FR^(+)CTC) and the benign or malignant lesions of the lung, and to establish a malignant prediction model for pulmonary neoplasm based on clinical data, imaging and FR^(+)CTC tests. Methods A retrospective analysis was done on 1 277 patients admitted to the Affiliated Hospital of Qingdao University from September 2018 to December 2019, including 518 males and 759 females, with a median age of 57(29-85) years. They underwent CTC examination of peripheral blood and had pathological results of pulmonary nodules and lung tumors. The patients were randomly divided into a trial group and a validation group. Univariate and multivariate analyses were performed on the data of the two groups. Then the nomogram prediction model was established and verified internally and externally. Receiver operating characteristic(ROC) curve was used to test the differentiation of the model and calibration curve was used to test the consistency of the model. Results Totally 925 patients suffered non-small cell lung cancer and 113 patients had benign diseases in the trial group;219 patients suffered non-small cell lung cancer and 20 patients had benign diseases in the verification group.The FR^(+)CTC in the peripheral blood of non-small cell lung cancer patients was higher than that found in the lungs of the patients who were in favorite conditions(P<0.001). Multivariate analysis showed that age≥60 years, female, FR^(+)CTC value>8.7 FU/3 mL, positive pleural indenlation sign, nodule diameter, positive burr sign, consolidation/tumor ratio<1 were independent risk factors for benign and malignant lung tumors with a lesion diameter of ≤4 cm. Thereby, the nomogram prediction model was established. The area under the ROC curve(AUC) of the trial group was 0.918, the sensitivity was 86.36%, and the specificity was 83.19%. The AUC value of the verification group was 0.903, the sensitivity of the model was 79.45%, and the specificity was 90.00%, indicating nomogram model discrimination was efficient. The calibration curve also showed that the nomogram model calibration worked well. Conclusion FR^(+)CTC in the peripheral blood of non-small cell lung cancer patients is higher than that found in the lungs of the patients who carry benign pulmonary diseases. The diagnostic model of clinical stage Ⅰ non-small cell lung cancer established in this study owns good accuracy and can provide a basis for clinical diagnosis.