| Background Lung cancer(LC)is a malignant tumor with the highest mortality.Slow progress for LC early diagnosis and bad 5 year survival rate are deemed to be responsible for it.Autoantibodies related to LC are becoming research hotspot in recent years,due to their existence in sera of LC patients 5 years prior to the onset of clinical symptoms.Aim In our previous research based on high-throughput protein chip screening followed by focused array validation,8 Ig G antoantibodies were successfully identified to be valuable biomarkers for early LC diagnosis,of which 3 antoantibodies panel including anti-TP53,ETHE1 and HRAS had 50% sensitivity and >90% specifity for early LC.Interestingly,4 autoantibodies panel including anti-TP53,HRAS,CTAG1 A and NSG1 were found to show good diagnostic performance with 56.50% sensitivity and 91.00% specifity for early LC through ELISA detection in a small cohort.As a result,we will explore the separate and combined diagnostic performance of 4 autoantibodies for early LC with different pathological types intensively in a large cohort,and then,the same will do with 5 traditional tumor markers including CEA,CYFRA21-1,SCCAg,NSE and PROGRP.Subquently,the differences of diagnostic performance for early LC with different pathological types between 4 autoantibodies panel and 5 tumor markers panel will be compared.Finally,we will pave the way for the elevation of diagnostic performance for early LC with different pathological types by the establishment of a panel including 4 autoantibodies combined with some tumor markers.Methods 1.The validation of ELISA results of anti-TP53,HRAS,CTAG1 A and NSG1 by western blot.2.The investigation of the separate and combined diagnostic performance of 4 autoantibodies for early LC with different pathological types in a large cohort by ELISA detection.4 Autoantibodies were detected by ELISA with TP53,HRAS,CTAG1 A and NSG1 A protein provided by the high-throughput center in John.Hopkins medical school in a large cohort comprised of 174 early LC patients,226 late LC patients,118 lung benign lesion(LBL)patients and 173 healthy controls(HC).The separate and combined diagnostic performance including area under curve(AUC),sensitivity and specificity of 4 autoantibodies for early LC with different pathological types were investigated and compared.3.5 traditional tumor markers including CEA,CYFRA21-1,SCCAg,NSE and PROGRP in the same cohort were detected by chemiluminescence method.The separate and combined diagnostic performance including AUC,sensitivity and specificity of 5 traditional tumor markers for early LC with different pathological types were investigated and compared.4.The differences of AUC,sensitivity and specificity for early LC with different pathological types between 4 autoantibodies panel and 5 tumor markers panel were compared.Furthermore,a panel including 4 autoantibodies combined with some tumor markers was investigated to elevate the diagnostic sensitivity for early LC with different pathological types without cutting essential specificity.Results 1.The results detected by western blot were the same as that of ELISA.2.The separated and combined diagnostic performance of 4 autoantibodies for early LC with different pathological types The highest positive rates of 4 autoantibodies in LBL group and HC group were only 7.63% and 2.89%,respectively.The AUCs of anti-TP53,CTAG1 A and NSG1 for early small cell lung cancer(SCLC)were >0.600,of which anti-TP53 had the highest AUC(0.703)and 44.74% sensitivity.The AUCs of all 4 autoantibodies for early lung squamous cell carcinoma(SCC)were >0.600,of which anti-CTAG1 A had the highest AUC(0.676)and 40.00% sensitivity.The AUCs of anti-TP53 and anti-HRAS for early lung adenocarcinoma(AD)were >0.600,of which anti-TP53 had the highest AUC(0.625)and 29.07% sensitivity.The AUCs of 4 autoantibodies panel for early SCLC,SCC and AD were 0.863,0.822 and 0.674 respectively.3.The separate and combined diagnostic performance of 5 tumor markers for early LC with different pathological types The AUCs of PROGRP,NSE,CEA and CYFRA21-1 for early SCLC were >0.600,of which PROGRP had the highest AUC(0.871),76.32% sensitivity and 97.46% specificity(vs LBL group),and NSE had the second leading AUC(0.778),63.16% sensitivity and 85.89% specificity(vs LBL group).The AUCs of CYFRA21-1 and SCCAg for early lung squamous cell carcinoma(SCC)were >0.700,of which CYFRA21-1 had the highest AUC(0.766).The AUCs of all 5 tumor markers for early lung adenocarcinoma(AD)were < 0.600,of which CYFRA21-1 had the highest AUC(0.570)and 26.74% positive rate(vs LBL group,P>0.05),and CEA had the second leading AUC(0.564),19.77% positive rate(vs LBL group,P>0.05).The AUCs of 5 tumor markers panel for early SCLC,SCC and AD were 0.846,0.769 and 0.627 respectively.4.The comparison of the diagnostic performance for early LC between 4 autoantibodies panel and 5 tumor markers panel There were no significant difference of AUCs for early LC with 3 pathological types between 4 autoantibodies panel and 5 tumor markers panel(P>0.05).The sensitivities of 4 autoantibodies panel for early SCLC ?SCC ?and AD were 84.21%?76.00% and 45.34%,respectively,which were not significantly different from that of 5 tumor markers panel(P>0.05).The positive rate of 4 autoantibodies panel in LBL group was 16.11%,which was significantly lower than that of 5 tumor markers panel(P<0.01).5.The diagnostic performance of 4 autoantibodies panel combined with some tumor markers for early LC The AUC of 4 autoantibodies panel combined with PROGRP was 0.908,which was the highest for early SCLC.The AUC of 4 autoantibodies panel combined with SCCAg was 0.818,which was the highest for early SCC.The AUCs,sensitivities and specificities for early AD of 4 autoantibodies panel combined with CEA and 4 autoantibodies panel combined with CYFRA21-1 and CEA,were 0.696 and 0.700,56.98% and 66.28%,82.13% and 73.54%,respectively.Conclusions 1.4 autoantibodies have good diagnostic performances for early SCLC and SCC,of which anti-TP53 and anti-CTAG1 A have the highest diagnostic performance for early SCLC and SCC,respectively.However,the sensitivities of 4 autoantibodies for early AD are not high enough.The combined detection of 4 autoantibodies might contribute to the elevation of diagnostic performance for early LC,which effects are especially prominent for early SCLC and SCC(AUC>0.800),but relatively insignificant for early AD(AUC<0.700).2.PROGRP and NSE have the ideal diagnostic performance for early SCLC,of which PROGRP has the highest AUC.CYFRA21-1 and SCCAg have good diagnostic performance for early SCC,of which CYFRA21-1 has the highest AUC.However,all diagnostic performances of 5 tumor markers are not good enough for early AD.There are no significant effects of combined detection of 5 tumor markers for the elevation of diagnostic performance for early LC with different pathological types.3.4 autoantibodies panel has equal sensitivity and better specificity as compared with 5 tumor markers panel.The establishment of 4 autoantibodies panel combined with some tumor markers might contribute to the elevation of diagnostic performance for early SCLC and AD,rather than early SCC. |
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