Clinical Study On Screening Of Early Non-small Cell Lung Cancer With Thioredoxin Reductase 1(TrxR1)

Objective: Thioredoxin reductase and its redox system(Trx R1)are closely related to the occurrence and development of lung cancer,breast cancer,renal cancer,prostate cancer and other cancers.Many studies have shown that Trx R1 and its system have high sensitivity and specificity in the diagnosis and prognosis evaluation of non-small cell lung cancer.but it has not yet met clinical needs,and the relationship with early lung cancer has not been clarified.Therefore,we designed a more clinical-oriented study to test the diagnostic efficacy of thioredoxin reductase in early non-small cell lung cancer for future clinical reference.Methods: From April 2019 to January 2020,a total of 150 patients who underwent surgical treatment of pulmonary nodules(maximum diameter ? 3cm)in the chest five disease area of the fourth hospital of Hebei Medical University were selected.Plasma Trx R1 activity and four clinical tumor markers(CEA,SCC,Cyfra21-1,NSE)were detected by fasting at least 10 hours before surgery.The diagnostic efficiency was calculated based on postoperative pathological results.Receiver operator characteristic curve(ROC)was used to analyze the true and false positive rate(sensitivity and 1-specificity),and the area under curve(AUC)was calculated to evaluate the efficacy of Trx R1 activity as a biomarker of non-small cell lung cancer(NSCLC).The maximum Youden index(sensitivity+specificity-1)was used to determine the best cut-off value of Trx R1 activity.Results:1.Plasma Trx R1 activity levels were measured in 110 patients with non-small cell lung cancer and 40 patients with benign pulmonary nodules.The results showed that the median Trx R1 value(8.15 U / ml)of NSCLC was significantly higher than that of benign pulmonary nodules(5.3 U / ml),and there was a significant statistical difference(Mann Whitney U test,P < 0.0001).2.There was no significant difference in Trx R1 activity among NSCLC patients with different nodule properties(Kruskal Wallis test,P = 0.480),infiltration degree(Mann Whitney U test,P = 0.327),and nodule size(Kruskal Wallis test,P = 0.719).3.Based on the ROC,Trx R1 plasma activity showed the highest area under the curve(AUC: 0.892),while the other four biomarkers performed poorly in the diagnosis of early non-small cell lung cancer.The area under the curve(AUC)of CEA is 0.622;the area under the curve(AUC)of SCC is 0.457;the area under the curve(AUC)of NSE is 0.518;the area under the curve(AUC)of Cyfra21-1 is 0.580.Based on the maximum Youden index,the optimal cutoff value for the plasma Trx R1 activity level in patients with non-small cell lung cancer and other patients with benign pulmonary sarcoidosis is 6.55 U / ml.The sensitivity was 80.0%,and the specificity was 85.0%.4.The area under the curve(AUC)for the diagnosis of non-small cell lung cancer by plasma Trx R1 activity in CEA-negative plasma Trx R1 was 0.883;the sensitivity was 78%;and the specificity was 84.6%.The area under the curve(AUC)for the diagnosis of non-small cell lung cancer by plasma Trx R1 activity in SCC-negative patients was 0.911;sensitivity was 82.4%;specificity was 86.1%.The area under the curve(AUC)for the diagnosis of non-small cell lung cancer by plasma Trx R1 activity in NSE-negative patients was 0.900;the sensitivity was 81.5%;and the specificity was 84.8%.The area under the curve(AUC)for the diagnosis of non-small cell lung cancer by plasma Trx R1 activity in Cyfra21-1 negative patients was 0.939;the sensitivity was 84.4%;and the specificity was 93.7%.5.Through the binary logistic equation,the CEA,SCC,NSE,and Cyfra21-1 were used for the diagnosis of early non-small cell lung cancer(AUC)at 0.650;sensitivity was 40.9%;specificity was 85.0%.We combined the four biomarkers with Trx R1 for the diagnosis of early non-small cell lung cancer(AUC)of 0.913;95% CI: 0.860-0.965;sensitivity of 95.5%;specificity of 72.5%.Conclusions:1.The expression of Trx R1 in early non-small cell lung cancer was significantly higher than that in patients with benign pulmonary nodules.Plasma Trx R1 expression level has high diagnostic value in patients with early non-small cell lung cancer.2.In the early stage of NSCLC,the nature,infiltration and size of pulmonary nodules did not affect the expression of Trx R1.3.The best cut-off value for the diagnosis of plasma Trx R1 activity level in patients with early non-small cell lung cancer and other patients with benign pulmonary sarcoidosis is 6.55 U / ml.Compared with the four biomarkers such as CEA,SCC,NSE and Cyfra21-1,plasma Trx R1 has higher diagnostic value for patients with early non-small cell lung cancer.4.For the negative NSCLC patients screened by CEA,NSE,SCC and CYFRA21-1,the detection of Trx R1 activity in plasma can improve the accuracy of diagnosis.5.The diagnostic accuracy of CEA,NSE,SCC and CYFRA21-1 combined with Trx R1 will be greatly improved.