Objective: To explore the value of detection of epidermal growth factor receptor (EGFR) gene amplification in peripheral blood rare cells in the assessment of benign and malignant pulmonary nodules. Methods: A total of 262 patients with pulmonary nodules were selected as the retrospectively study subjects from the Second Affiliated Hospital of Army Military Medical University and Peking Union Medical College Hospital from July 2022 to August 2023. There were 98 males and 164 females, with the age range from 16 to 79 (52.1±12.1) years. The EGFR gene amplification testing was performed on the rare cells enriched from patients' peripheral blood, and the clinical manifestations, CT imaging features, histopathological and/or pathological cytological confirmed results of patients were collected. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value of the method of detection of EGFR gene amplification in peripheral blood rare cells, and its diagnostic efficacy was evaluated. Results: Among the 262 patients, 143 were malignant pulmonary nodules and 119 were benign pulmonary nodules. The differences between malignant pulmonary nodules and benign pulmonary nodules in nodule diameter and nodule density were statistically significant (both P<0.001), while the differences in age, gender and nodule number were not statistically significant (all P>0.05). The number [M (Q1, Q3)] of EGFR gene amplification positive rare cells in patients with malignant pulmonary nodule was 8 (6, 11), which was higher than that in patients with benign pulmonary nodule [2 (1, 4), P<0.001]. The ROC curve results showed that when the optimal cut-off value was 5 (that was, the number of EGFR gene amplification positive rare cells was>5), the area under the curve (AUC) of the detection of EGFR gene amplification in peripheral blood rare cells for discrimination of benign and malignant pulmonary lesions was 0.816 (95%CI: 0.761-0.870), with a sensitivity of 83.2%, a specificity of 80.7%, and an accuracy of 82.1%. Based on the analysis of the diameter of the nodules, the AUC for distinguishing between benign and malignant pulmonary nodules with diameter 5-9 mm and 10-30 mm was 0.797 (95%CI: 0.707-0.887) and 0.809 (95%CI: 0.669-0.949), respectively, with sensitivity, specificity and accuracy reached 75% or above. Based on the analysis of nodule density, the AUC for distinguishing between benign and malignant solid nodule and subsolid nodule was 0.845 (95%CI: 0.751-0.939) and 0.790 (95%CI: 0.701-0.880), respectively, with sensitivity, specificity and accuracy reached 75% or above. Based on the analysis of nodule number, the AUC for distinguishing between benign and malignant solitary pulmonary nodule and multiple pulmonary nodule was 0.830 (95%CI: 0.696-0.965) and 0.817 (95%CI: 0.758-0.877), respectively, with sensitivity, specificity and accuracy reached 80% or above. Conclusion: The detection of EGFR gene amplification in peripheral blood rare cells contributes to the evaluation of benign and malignant pulmonary nodules, and can be used in the auxiliary diagnosis of benign and malignant pulmonary nodules.
目的： 探讨外周血稀有细胞表皮生长因子受体（EGFR）基因扩增检测在肺结节良恶性评估中的价值。 方法： 回顾性选取陆军军医大学第二附属医院、北京协和医院2022年7月至2023年8月就诊的262例肺结节患者作为研究对象，其中男98例，女164例；年龄16~79（52.1±12.1）岁。对患者进行外周血稀有细胞EGFR基因扩增检测，并收集患者临床表现、CT影像学特征、病理组织学确诊结果和（或）病理细胞学确诊结果。应用受试者工作特征（ROC）曲线确定外周血稀有细胞EGFR基因扩增检测方法的cut-off值，评估其诊断肺结节良恶性的效能。 结果： 262例患者中，恶性肺结节143例，良性肺结节119例。恶性和良性肺结节组结节直径和结节密度差异均有统计学意义（均P<0.001）；年龄、性别和结节数量差异均无统计学意义（均P>0.05）。恶性肺结节组EGFR基因扩增阳性稀有细胞数量［M（Q1，Q3）］为8（6，11）个，高于良性肺结节组［2（1，4）个，P<0.001］。ROC曲线结果显示，cut-off值为5时（即EGFR基因扩增阳性稀有细胞数>5个时），外周血稀有细胞EGFR基因扩增检测鉴别肺部良恶性病变的曲线下面积（AUC）为0.816（95%CI：0.761~0.870），灵敏度为83.2%，特异度为80.7%，准确度为82.1%；直径5~9 mm和10~30 mm肺结节良恶性鉴别的AUC分别为0.797（95%CI：0.707~0.887）和0.809（95%CI：0.669~0.949），灵敏度、特异度和准确度均>75%；实性肺结节和亚实性肺结节良恶性鉴别的AUC分别为0.845（95%CI：0.751~0.939）和0.790（95%CI：0.701~0.880），灵敏度、特异度和准确度均>75%；单发肺结节和多发肺结节良恶性鉴别的AUC分别为0.830（95%CI：0.696~0.965）和0.817（95%CI：0.758~0.877），灵敏度、特异度和准确度均≥80%。 结论： 外周血稀有细胞EGFR基因扩增检测有助于肺结节的良恶性评估，可用于辅助诊断肺结节的良恶性。.