Expression And Diagnostic Siginificance Of Plasma LncRNA ZFAS1 In Non-small Cell Lung Cancer

Objective:1.Detect the expression level of Long non-coding RNA(Lnc RNA)zine finger antisense1(ZFAS1)in plasma from patients with non-small cell lung cancer(NSCLC)and lung benign disease.2.Evaluate the diagnostic value of plasma Lnc RNA ZFAS1 on NSCLC.3.Investigate the association between the expression level of Lnc RNA ZFAS1 in and clinical features in patients with NSCLC.4.Explore the correlation between the expression level of Lnc RNA ZFAS1 in tumor tissues and prognosis of in NSCLC patients.Methods:1.In total,60 plasma samples from primary NSCLC patients and 60 plasma samples from patients with lung benign disease were collected.All subjects were recruited in the Department of Respiratory and Critical Care Medicine,Gansu Provincial Hospital during November 2021 and October 2022.2.The expression level of Lnc RNA ZFAS1 in plasma were detected by Quantitative real-time PCR(q RT-PCR).The association between the expression level of Lnc RNA ZFAS1 in plasma and clinicopathologic features in patients with NSCLC and common clinical serum tumor markers was statistically analyzed.3.The receiver operating characteristic curve(ROC)was used to evaluate the diagnostic value of plasma Lnc RNA ZFAS1,serum CEA,and CYFRA21-1 alone,and the combination of all three on NSCLC.4.The Kaplan-Meier Plotter online analysis database was used to explore the correlation between Lnc RNA ZFAS1 levels in tumor tissues and prognosis of patients with NSCLC.Results:1.Lnc RNA ZFAS1 was detected in the plasmas of NSCLC patients and patients with lung benign disease.The expression of Lnc RNA ZFAS1 was significantly down-regulated in plasmas of NSCLC patients compared to lung benign disease group(P<0.05).2.The expression of Lnc RNA ZFAS1 in plasma of NSCLC patients was negatively correlated with the expression of serum CYFRA21-1,SCCA,CEA,CA125 and CA199(r=-0.493,-0.191,-0.549,-0.511,-0.427,P<0.05),and was not associated with the expression of serum Pro GRP and NSE(P>0.05).3.The area under receiver operating characteristic curve(AUC)of plasma Lnc RNA ZFAS1 for diagnosis of NSCLC was 0.872(95%CI:0.799-0.926),the sensitivity and specificity were81.7% and 76.7%,respectively.The AUC of serum CEA for diagnosis of NSCLC was 0.812(95%CI:0.730-0.877),the sensitivity and specificity were 73.7% and 81.7%,respectively.The AUC of serum CYFRA21-1 for diagnosis of NSCLC was 0.801(95%CI : 0.717-0.868),the sensitivity and specificity were 66.7% and 89.8%,respectively.The sensitivity of plasma Lnc RNA ZFAS1 was higher than serum CEA and CYFRA21-1,but the specificity was lower.4.After combination of plasma Lnc RNA ZFAS1,CEA and CYFRA21-1,the AUC,sensitivity and specificity of these three markers for diagnosis of NSCLC were 0.902(95%CI:0.834-0.949),76.7% and 96.9%,respectively.Compared with the diagnosis alone,the AUC of comprehensive diagnosis was highest,the specificity,positive predictive and accuracy were improved when the sensitivity and negative predictive value were well maintained.5.The expression level of Lnc RNA ZFAS1 in plasma of NSCLC patients was significantly correlated with maximum tumor diameter,TNM stage,lymph node metastasis and distant metastasis(P<0.05),but was not related to gender,age,smoking history,pathological type and the mutations of EGFR,ALK and KARAS(P>0.05).6.The Kaplan-Meier Plotter online analysis database showed that in general,the overall survival rate of NSCLC patients with low Lnc RNA ZFAS1 expression in tumor tissues was significantly higher than that of patients with high expression(HR=1.9,logrank P <0.05).For lung adenocarcinoma patients,the overall survival rate of patients with low Lnc RNA ZFAS1 expression was significantly higher than that of patients with high expression(HR = 2.48,logrank P<0.05).The overall survival rate of patients in I-II stages with low Lnc RNA ZFAS1 expression was significantly higher than that of patients with high expression(HR = 4.27,logrank P<0.05).Conclusions:Compared to lung benign disease group,the expression level of Lnc RNA ZFAS1 was significantly down-regulated in the plasma of NSCLC patients.The sensitivity of Lnc RNA ZFAS1 in the diagnosis of NSCLC was higher than that of serum CYFRA21-1 and CEA.Compared to plasma Lnc RNA ZFAS1,serum CYFRA21-1 and CEA alone,the combination of all three could improve the diagnostic efficacy of NSCLC.The expression level of Lnc RNA ZFAS1 in tumor tissue can predict the prognosis of NSCLC patients.Lnc RNA ZFAS1 is expected to be a novel plasma marker for the diagnosis of NSCLC.