| Research background and purpose:Thymidine kinase 1(TK1)is one of the key enzymes of the pyrimidine rescue synthesis pathway in the cell proliferation cycle.When the cell is malignant,TK1 is released from the proliferating malignant cells.The degree of destruction of the malignant cells can be measured by measuring the concentration of TK1 in the extracellular fluid,which can be used as a new specific marker of cell proliferation.This study explored the value of serum thymidine kinase 1 in benign and malignant pulmonary nodules,combined with traditional tumor markers(CEA,NSE,CYFRA21-1)and chest CT features for the diagnosis of early lung cancer,and provided an important reference for clinically identifying benign and malignant pulmonary nodules.Materials and Methods:A total of 120 patients with pulmonary nodules who were first diagnosed in our hospital’s thoracic surgery from November 1,2018 to October 31,2019 were collected,and 70 cases of pulmonary malignant nodules were confirmed by pathology after surgery,and 50 cases of benign nodules.Blot chemiluminescence method was used to detect the expression level of thymidine kinase 1 in patients with benign and malignant pulmonary nodules,and chemiluminescence immunoassay was used to detect the expression levels of tumor markers CEA,NSE and CYFRA21-1 in patients with benign and malignant pulmonary nodules.The imaging characteristics of patients with chest plain scan and enhanced CT before surgery were collected,and the differences in serum TK1,CEA,NSE,and CYFRA21-1 expressions in patients with benign and malignant pulmonary nodules were compared,and the differences in chest CT imaging characteristics between the two groups were compared(nodule location,size,density,morphology,burr sign,lobular sign,vascular sign,bronchial sign,air sign,and pleural depression sign),serum TK1,CEA,NSE,CYFRA21-1 alone and combined in the diagnosis value of benign and malignant pulmonary nodules,the independent risk factors of malignant pulmonary nodules were screened out by Logistic regression analysis,so as to establish a diagnostic predictive model of benign and malignant pulmonary nodules and test its diagnosis value.Result:1.In this study,there were 120 patients with pulmonary nodules,70 with malignant nodules,accounting for 58.3%of all nodules,including 12 squamous cell carcinomas and 58 adenocarcinomas;50 benign nodules,accounting for about 41.7%,of which There were 6 cases of hamartoma,12 cases of tuberculous granuloma,1 case of sclerosing hemangioma,1 case of diffuse lymphocyte hyperplasia,and 30 cases of inflammatory pseudotumor.2.The average age of patients with benign and malignant pulmonary nodules was58.64±12.61 years and 60.33±9.69 years(P=0.079).Among the benign pulmonary nodules,there were 22 males,accounting for 44%of all benign pulmonary nodules,and28 females,accounting for 56%.Among the malignant pulmonary nodules,39 were male,accounting for approximately 55.7%of all malignant pulmonary nodules,and 31were female,accounting for approximately 44.3%(P=0.208).34%of patients with benign pulmonary nodules were smokers,while approximately 48.6%of patients with malignant nodules were smokers(P=0.143).There were no significant differences in age,gender,and smoking history between the two groups of patients with benign and malignant pulmonary nodules(P=0.079,P=0.208,P=0.143).3.Through a univariate analysis of chest CT characteristics of the two groups of patients,it was found that there were statistically significant differences in imaging features such as lung nodule size,nodular morphology,burr sign,defoliation sign,vascular sign,bronchial sign,and pleural depression sign(P<0.05).4.The serum TK1 expression level in the malignant pulmonary nodule group was2.02(1.65,2.43)pM,which was significantly higher than that in the benign pulmonary nodule group(1.28(0.84,1.74)pM,P<0.0001);In the benign and malignant pulmonary nodules,the serum CEA expression levels were 1.22(0.82,2.20)ng/ml,2.22(1.46,3.89)ng/ml(P=0.0258),and the levels of CYFRA21-1 were 0.93(0.44,1.60)ng/ml and 2.00(0.90,3.30)ng/ml(P=0.0004),there was a statistical difference in serum TK1,CEA,and CYFRA21-1 between the two groups(P<0.05).5.ROC curve analysis showed that serum TK1,CEA,and CYFRA21-1 were used alone in the diagnosis of malignant pulmonary nodules,the sensitivity was 84.29%,87.14%,and 58.57%,the specificity was 68%,52%,and 76%,and the AUC was 0.783,0.752,and 0.711.When the three were combined,the sensitivity for diagnosing malignant pulmonary nodules was 81.43%,the specificity was 74%,and the AUC was0.833.6.Multivariate Logistic regression analysis showed that there were statistical differences in serum TK1,serum CEA,nodular morphology,and bronchial sign(P<0.05),which were independent predictors of malignant pulmonary nodules.Establish a predictive model of malignant pulmonary nodules:P=e~x/(1+e~x),X=–4.629+(1.199×TK1)+(0.619×CEA)+(–1.963×bronchial sign)+(2.258×nodule morphology),The results of testing the diagnostic efficacy of the model show that the sensitivity is87.14%,the specificity is 82%,the AUC is 0.910,and the Hosmer-Lemeshow goodness-of-fit test shows that:χ~2=7.807,P=0.453>0.05,the results show that Model has good prediction accuracy in the diagnosis of benign and malignant pulmonary nodules.Conclusion:1.Patients with malignant pulmonary nodules have significantly higher serum TK1 levels than patients with benign pulmonary nodules,which can be used as a potential serum biomarker for the diagnosis of lung cancer.2.By combining serum TK1,CEA and CYFRA21-1,the accuracy of malignant pulmonary nodules can be improved.3.In this study,by combining the clinical characteristics,imaging characteristics,and serum tumor markers of patients,a prediction model for malignant pulmonary nodules was established,which has good sensitivity and specificity for the diagnosis of malignant pulmonary nodules,and will improve the accuracy of early lung cancer diagnosis. |
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