| Objective:Lung cancer is one of the most common malignant tumors in China,and the leading cause of cancer-related death worldwide.One of the main reasons of the high mortality is most lung cancers can only be identified at a late stage as the early lung cancers often has no obvious clinical symptoms but only imaging manifestations.In recent years,the wide use of Low-Dose Computed Tomography(LDCT)has significantly increased the detection rate of early lung cancer,but also greatly improved the detection rate of pulmonary nodules.One type of specific pulmonary nodules is characterized by solitary pulmonary nodule(SPN).A certain proportion of these SPNs are malignant lesions,and how to distinguish between benign and malignant SPNs is timely.Identifying malignant lesions and avoiding over-treatment of benign lesions has become an important issue for many clinicians.At present,there is no reliable biomarker to identify benign and malignant pulmonary nodules in the early stage of the disease.Studies have shown that malignant tumors can release circulating tumor cells(CTC)into the blood at the very early stage of the disease.The detection of CTC has also played an important role in the early diagnosis of some solid tumors.The folate receptor(FR)-targeted PCR method can detect the CTC in the blood of patients with lung cancer.However,there is no research to explore the diagnostic value of this method in judging the benign and malignant solitary pulmonary nodules.The purpose of this study was to evaluate the effectiveness and feasibility of detecting CTC for the diagnosis of benign and malignant solitary pulmonary nodules by FR-targeted PCR.Methods:This study was a prospective analysis of 79 newly diagnosed solitary pulmonary nodules patients admitted to the Department of Respiratory and Critical Care Medicine,JinLing Hospital from April 2016 to August 2016.All patients were given 4 ml of venous blood on the day of the visit.CTCs in the blood were detected by FR-targeted PCR technique within 24 hours,and CTC levels were recorded.The patients were followed up for two years.After the follow-up,patients were divided into malignant group(39 patients),pathologically diagnosed benign group(11 patients)and imaging benign group(29 patients).CTC levels were compared between the three groups.Patients with malignant lesions were further divided into AAH group(3 persons),AIS group(6 persons),stage Ⅰ(21 persons),stage Ⅱ(1 person)and stageⅣ(3 persons)according to the pathological stage of lung cancer and the 8th edition of lung cancer TNM stage,and the CTC levels were compared between patients in different stages.The last,the cutoff value of this method for distinguishing benign and malignant SPNs and its sensitivity and specificity for the diagnosis of malignant SPNs were determined by ROC curve.Results:The CTC level of lung cancer patients was 10.75 ± 8.03 folate units/3ml,and the pathological diagnosis of benign patients was 8.10 ± 4.90 folate units/3ml.The CTC level of imaging diagnosis of benign patients was 6.91 ± 3.60 folate units/3ml.The CTC level of lung cancer patients was higher than that of patients with pathological diagnosis of benign disease and the imaging diagnosis of benign disease(P<0.001).In patients with lung cancer,the CTC level of patients with stage Ⅳ was significantly higher than that of patients with stage Ⅰ and AAH.The ROC curve analysis indicated that the sensitivity of the CTC for the diagnosis of malignant pulmonary nodules using the FR-targeted PCR method was 70.0%and the specificity was 71.4%with the cutoff value of 8.81 folate units/3ml,and the AUC was 0.731(95%CI:0.621-0.840).This method is more diagnostic for SPNs with solid and partially solid imaging findings,with sensitivity and specificity of 85.0%and 75.0%,respectively.Conclusion:FR-positive CTCs were feasible diagnostic biomarkers in patients with malignant SPNs,especially in patients with solid and partially solid SPNs.The level of CTCs is related to the stage of lung cancer. |
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