Application Value Of Autoantibodies Against Tumor-associated Antigen In Diagnosis Of Early Non-small Cell Lung Cancer

Background: Lung cancer is the most incidence and mortality of malignant tumor in male,and accounts for the vast majority.Early diagnosis can significantly improve the survival rate of lung cancer,but lung cancer is usually hard to diagnose at early stage,and only about 16% of lung cancer is limited to the primary site during diagnosis.The method for early diagnosis of non-small cell lung cancer(NSCLC)is of great significance.Screening by computed tomography(CT)can help identify early lung cancer lesions and reduce lung cancer mortality.However,low-dose CT examination has its limitations,such as additional invasive examinations caused by higher false positive rates can increase burden of patients,delay treatment due to false negatives,and radiation risks.At the time of tumorigenesis,the human immune system can recognize tumor-associated antigens(TAAs)to produce autoantibodies.When TAAs appear,they exhibit corresponding effective biological amplification.And autoantibodies have already appeared before TAAs can be detected,and this secretion is before the appearance of the first clinical symptoms.Compared to other potential biomarkers,autoantibodies persist relatively stable in the blood which can be easily obtained.Autoantibodies has the potential to be an early lung cancer screening marker.Objective: Comparing the expression levels of autoantibodies against LAMR1,p53,ENO1 a,ENO1b,IMPDH1 a and IMPDH2 a in serum between NSCLC patients and healthy controls.Investigating the expression characteristics of TAAs autoantibodies in different stages of tumors,revealing their specificity in early NSCLC.Investigating the diagnostic efficacy of TAAs autoantibodies in all stages and in stage I NSCLC to clarify the diagnostic value in early NSCLC.Methods:In this study,we used the immunoinformatics database(IMGT database,IMGT/HLA database,T cell epitope query and prediction database and HLA epitope binding prediction tools)and immunology software to calculate and synthesize peptide antigens of tumor-associated antigens LAMR1,p53,ENO1 a,ENO1b,IMPDH1 a and IMPDH2 a.A total of 146 NSCLC and 141 healthy controls cases were enrolled in the study.The level of autoantibodies in the serum was determined by ELISA and the specific binding index(SBI)was calculated.SPSS21.0 was used for statistics analysis.The expression levels of six TAAs autoantibodies in NSCLC patients and healthy controls were analyzed.The different expression of TAAs autoantibodies in early and late stages of tumor were analyzed.The differences of expression levels between stage I lung cancer,healthy and advanced patients were further compared.The diagnostic efficacy of six TAAs autoantibodies in all NSCLC patients and stage I NSCLC was evaluated by positive rate test and ROC analysis.Results: 1.The levels of autoantibodies against six TAAs in NSCLC patients were significantly higher(P<0.001).2.The expression levels of autoantibodies against six TAAs in the serum of patients with early NSCLC were higher than those of patients in late stage NSCLC.Among them,LAMR1 and p53 autoantibody levels were significantly higher in patients with early stage(P<0.05).3.The autoantibody levels against six TAAs in patients with stage I NSCLC were significantly higher than those in healthy individuals(P<0.001),the mean level of autoantibodies against six TAAs were higher in stage I than in stage III/IV lung cancer patients.But only the difference between LAMR1 and p53 was statistically significant(P<0.05).4.The positive rates of autoantibodies against LAMR1,p53,ENO1 a,ENO1b,IMPDH1 a,and IMPDH2 a in NSCLC patients were 17.81%,17.12%,31.51%,21.23%,23.97%,and 6.16%,respectively.The positive rates of autoantibodies against LAMR1,p53,ENO1 a,ENO1b,IMPDH1 a,and IMPDH2 a in stage I NSCLC were 21.15%,26.92%,32.69%,21.15%,23.08%,and 5.77%,respectively.5.Compared with healthy individuals,the AUC of single TAAs autoantibodies in NSCLC was 0.675 to 0.723,sensitivity was 24.0% when specificity is 90%,positive predictive value was 56.52% to 86.79%,and negative predictive value 49.45% to 57.26%.The AUC of the combined six TAAs was 0.739(95% CI: 0.682-0.796),with a specificity of 47.3% at 90% specificity,the positive predictive value was 85.11% and the negative predictive value was 55.83%.A good diagnostic performance of TAAs autoantibodies was shown.6.The AUC of single TAAs autoantibody in stage I NSCLC was 0.705 to 0.805.The sensitivity was 28.8% to 53.8% when specificity was 90%,the positive predictive value was 30.00% to 70.83%,and the negative predictive value was 77.01% to 79.29%.The AUC of the combined six TAAs was 0.817(95% CI: 0.749-0.885),with a specificity of 53.8% at 90% specificity,the positive predictive value was 66.67%,and the negative predictive value was 77.91%.It was shown that TAAs autoantibodies have higher diagnostic efficacy in stage I NSCLC.Conclusion: 1.Serum levels of autoantibody against LAMR1,p53,ENO1 a,ENO1b,IMPDH1 a and IMPDH2 a were highly expressed in NSCLC patients.2.The increased autoantibody expression levels of LAMR1,p53,ENO1 a,ENO1b,IMPDH1 a,and IMPDH2 a of NSCLC patients mainly concentrated in the early stage.3.The autoantibodies against six TAAs have been highly expressed in stage I NSCLC.In the late stage of the NSCLC showed a downward trend.4.The six TAAs autoantibodies had high positive expression rates in NSCLC sepecially in stage I NSCLC.5.The six TAAs and combination of them can distinguish NSCLC cases from healthy controls with a higher sensitivity and specificity.6.The six TAAs autoantibodies and combined detection are more sensitive in the diagnosis of stage I NSCLC,indicating that TAAs autoantibodies have good potential as biomarkers of early NSCLC diagnosis.