The Clinical Value Of Genetically Abnormal Circulating Cells In The Differential Diagnosis Of Pulmonary Nodules

BackgroundLung cancer ranks first in the number of new cases and deaths of malignances in China.Non-small cell lung cancer（NSCLC）accounts for about 85% of the total number of lung cancer cases.Most of the early-stage lung cancers manifested as pulmonary nodules radiologically.With the popularization and application of low dose computed tomography（LDCT）in lung cancer screening,the detection rate of lung nodules has significantly increased,makes the diagnosis of pulmonary nodules an important issue yet there is still limit effective methods.Recently,the concept of genetically abnormal circulating cells（CACs）has brought new ideas for the diagnosis of benign and malignant pulmonary nodules.However,the clinical value of CACs in the differential diagnosis of pulmonary nodules and its correlation with clinicopathological and imaging features of patients with malignant pulmonary nodules are still unclear,which needs to be further studied.ObjectiveTo explore the clinical value of CACs in the differential diagnosis of pulmonary nodules as well as the correlation between the existence of CACs and the clinicopathological and imaging features of patients with malignant pulmonary nodules.Furthermore,the risk factors of malignant pulmonary nodules were analyzed based on the CACs,serum tumor markers,clinical and imaging characteristics.Methods220 pulmonary nodules patients with a definite diagnosis in Henan Provincial People’s Hospital from December 2019 to December 2020 were enrolled.The patients were divided into malignant nodule group（Lung Cancer Group）and benign nodule group（benign lung disease group）.The peripheral venous blood of patients was taken before surgery to detect the levels of CACs and serum tumor markers,such as CEA,SCC-Ag,CYFRA21-1,NSE respectively,and to analyze the sensitivity,specificity and accuracy of CACs in the differential diagnosis of benign and malignant pulmonary nodules with receiver operating characteristic curve,ROC;At the same time,the clinicopathological and imaging data of patients were collected to analyze the correlation between the level of CACs and the clinicopathological and imaging characteristics of patients with malignant pulmonary nodules.Level of circulating CACs,serum tumor markers,clinical and imaging characteristics were included in the univariate analysis,and the variables with P < 0.1 were further included in the binary logistic regression analysis to establish the independent risk factors related to malignant pulmonary nodules.Results1.A total of 220 patients were enrolled,89 have benign nodules and 131 have malignant ones.There was no significant difference in age,sex,smoking history,family history of tumor and history of respiratory diseases between two groups.（P > 0.05）;2.Nodule size,number,lobulation sign,spiculated sign,pleural traction sign and vascular bundle sign（P < 0.05）significantly varied between two groups;There was no significant difference with nodule location,type and vacuole sign（P > 0.05）;3.CACs were detected in 122（93.1%）of 131 patients with malignant pulmonary nodules,with a median of 4（3,7）/ 2.5ml peripheral blood;CACs were detected in 52（58.4%）of 89 patients with benign pulmonary nodules,with a median of 1（0,2）/ 2.5ml peripheral blood;The number of CACs in malignant nodule group was significantly higher than that in benign group,and the difference between the two groups was statistically significant（P < 0.001）;4.The sensitivity,specificity,accuracy,positive predictive value,and negative predictive value of malignant pulmonary nodules were 81.7%,76.4%,79.5%,83.6% and 73.9%,respectively with 3/2.5ml peripheral blood as cut-off value.The AUC under the ROC curve of CACs to distinguish benign and malignant pulmonary nodules was 0.826（95% CI,0.771 –0.882;P < 0.001）;5.The sensitivity and accuracy of CACs in pure ground glass nodules and mixed ground glass nodules were higher than those of solid nodules.The larger nodules group also have a higher diagnostic accuracy of CACs as well as a larger AUC（P < 0.001）;6.There was no significant difference in the distribution of CACs in patients with different pathological types and stages（P > 0.05）;7.The level of CACs was significantly correlated with the size of malignant pulmonary nodules（P < 0.05）.There was no significant correlation with the clinical features,other chest CT features,pathological types and pathological stages of patients with malignant pulmonary nodules（P > 0.05）;8.The AUC value of CACs in the differential diagnosis of benign and malignant pulmonary nodules was greater than that of serum tumor markers alone or combined detection;The detection of CACs combined with serum tumor markers can further improve the AUC value of malignant pulmonary nodules;9.Binary logistic regression analysis showed that CACs,CEA,age,lobulation sign and vascular cluster sign were independent risk factors related to malignant pulmonary nodules.The OR was 14.281（95% CI 5.903-34.548,P < 0.001）for CACs when the cut-off was set to≥3/2.5ml peripheral blood;The OR was 5.437（95% CI 1.790-16.513,P = 0.003）for serum CEA（≥ 5ng / ml）and 2.768（95% CI 1.171-6.544,P = 0.020）for age（≥ 60 years old）,2.729（95% CI 1.120-6.653,P = 0.027）for lobulation sign and 3.819 for vascular bundle sign（95%CI 1.596-9.141,P = 0.003）.Conclusions1.CACs have significant clinical value in the differential diagnosis of benign and malignant pulmonary nodules,and can be used as potential biomarkers for the diagnosis of early lung cancer;2.The level of CACs was significantly correlated with the size of malignant pulmonary nodules,but not with clinicopathological features;3.CACs,CEA,age,lobulation sign and vascular bundle sign were independent risk factors for malignant pulmonary nodules,among which CACs was the main risk factor.