Evaluation Of The Diagnostic Value Of Autoantibodies To Tumor-associated Antigens For Lung Cancer

BackgroundThe morbidity and mortality of lung cancer(LC)rank ahead among all of the malignant tumors worldwide.The healthy and development of human also heavily suffered from LC.Most lung cancer patients were diagnosed at advanced stage and missed the best opportunity for operating due to the lack of typical features and an efficient method in screening.The five years survival rate is only 15%,so it is vital to search a more reliable method to detect LC at early stage for improving the prognosis of patients with LC.The methods which were used to screen LC patients in clinical can’t provide credible result due to the low sensitivity and specificity,such as sputum cytology screening,tumor markers,inclusion of sediment from pleural effusion,X-rays,high resolution chest tomography(HRCT)and low-dose chest tomography(LDCT).Therefore,the pathological examination remains the “golden standard” of lung cancer diagnosis.Invasion and uneconomic expenditure make it difficult to be accepted and widely utilized.Hence,it is urgent to find an efficient,simple,inexpensive method with enough sensitivity and specificity to screen LC.As we all know,autoantibody against tumor-associated antigens(TAAs)is a kind of specific antibody that generated by immune response to the abnormally expressed tumorantigens.Besides,it could be detected months ahead of symptom occurrence and it would stably persist a long time after the antigens disappeared.Consequently,autoantibody might be one kind of potential biomarker for the diagnosis of LC.ObjectiveSerum levels of anti-CK5,anti-CK7,anti-Napsin A,anti-P63 and anti-TTF-1 in patients with LC and normal subjects were detected by Enzyme-Linked Immunosorbent Assay(ELISA).We analyzed the diagnostic value of single autoantibody in LC and non-small cell lung cancer(NSCLC).Multiple biomarkers were combined to compare the diagnostic value of LC.Furthermore,the correlation between autoantibodies in serum and corresponding proteins in tissue was also investigated.Methods1.Study participants were enlisted from the First Affiliated Hospital of Zhengzhou University.254 LC patients were recruited from October 2016 to January2017.222 healthy individuals with health examination were obtained in May 2019.2.Five proteins(CK5,CK7,Napsin A,P63,TTF-1)commonly detected in tissue from patients with LC to distinguish adenocarcinoma and squamous carcinoma were selected as target-antigens.The levels of corresponding autoantibodies in the serum of LC patients and healthy controls were detected by ELISA.Meanwhile,the optical density(OD)value,which satisfied the premise of specificity≥90% and possessed the highest Youden index,was regarded as the cutoff value to determine positive response.3.Serum levels and positive rate of five autoantibodies between LC group and NC group were compared.Those statistical indicators that were used to evaluate the diagnostic performance for LC also were computed,such as sensitivity,specificity,accuracy,positive predictive value,negative predictive value,positive likelihood ratio,negative likelihood ratio and area under curve(AUC).4.Serum expression level and positive rate of single autoantibody betweenNSCLC group and NC group were compared,and AUC was used to evaluate the diagnostic efficiency of NSCLC.5.The correlation between autoantibody and different clinical characteristics were analyzed through evaluating the differences of serum levels and positive rate of autoantibodies in patients with different genders,ages,history of smoking,clinical stage,pathological type,lymph metastasis,distant metastasis.6.The diagnostic capacity with multiple biomarkers in screening LC were also explored.7.Serum levels and positive rate of the corresponding autoantibody in patients with different expression of tumor-associated protein were compared to prove the correlation between them.Results1.Serum levels and positive rate of anti-CK5,anti-CK7,anti-Napsin A,anti-P63 and anti-TTF-1 in LC group were significantly higher than those in NC group(P<0.05).The sensitivity in the diagnosis of LC ranged from 13.78% to 29.13%,and the accuracy ranged from 50.21% to 57.56%,respectively.To some extent,five autoantibodies had good diagnostic value in LC,of which anti-CK7 might be the optimal biomarker with AUC of 0.707(95%CI: 0.660-0.753).2.Serum expression of anti-CK7,anti-p63,anti-TTF-1 in patients with LC were increased with tumor grade(P<0.05).The expression levels of five autoantibodies were not related to age,gender,history of smoking,lymph metastasis and distant metastasis(P>0.05).3.Serum levels and positive rate of five autoantibodies in NSCLC group were significantly higher than those in NC group,of which the differences of anti-CK5,anti-CK7,anti-P63 and anti-TTF-1 exist statistically significance(P<0.05).In the condition of specificity≥90%,anti-CK7 performed the best sensitivity(28.0%)and accuracy(59.82%).Five autoantibodies have some diagnostic value in NSCLC,of which anti-CK7 shown an AUC of 0.713(95%CI: 0.665-0.760),it might be the optimal biomarker.Additionally,serum levels and positive rate of five autoantibodiesbetween adenocarcinoma(ADC)and squamous cell lung cancer(SCC)were not statistically significant(P>0.05).4.Serum levels and positive rate of corresponding autoantibody had no statistically significance between patients with different expression of tumor-associated protein(P>0.05).5.Each autoantibody combined with CEA could be used to diagnose LC with AUC from 0.705(anti-CK5,CEA)to 0.770(anti-CK7,CEA).When five autoantibodies combined with CEA,the AUC for the diagnosis of LC reached up to0.784.The combination of anti-CK7,anti-TTF-1and CEA generated an AUC of0.785.Conclusions1.Five autoantibodies in serum have diagnostic value for LC,and might be used to screen patients with NSCLC.2.There was no association between serum level of autoantibody and the expression of corresponding protein.3.Anti-CK7 and anti-TTF-1 combined with tumor marker CEA could improve the diagnostic value for LC.