Study On Correlation Between Driver Genes Of Non-small Cell Lung Cancer And Clinical Traits, Tumor Markers In Chinese Population

Objective: This study aimed to evaluate the correlation between driver genes of non-small cell lung cancer(NSCLC)and tumor markers in Chinese population.Moreover,we conducted a meta-analysis based on the current studies on the relationship between epidermal growth factor receptor(EGFR)and tumor markers in Chinese NSCLC to support the result of our study,and to provide evidence for choosing target agents in clinical practice.Methods: 1.The analysis on clinical data We retrospectively collected 563 cases of NSCLC meeting included criteria at the First Affiliated Hospital of Fujian Medical University ranged from November 2012 to July 2018.Chi-square test was used to preliminarily assess the correlation between driver genes and clinical traits,tumor markers.If Chi-square test unavailable,Fisher’s test would be employed.Stratified analysis was performed according to the status of gender and smoking.Unconditional logistic regression analysis was conducted to further verify the relationship between driver genes of NSCLC and tumor markers.The clinical data was analyzed by SPSS 22.0.The value of two-tailed P <0.05 represented a statistical significance.2.Meta-analysis Pubmed,Embase,Cochrane Library,CNKI,Wanfang and VIP databases were thoroughly searched to identify the study on the correlation between EGFR of NSCLC and tumor markers in Chinese population and to perform this meta-analysis.The random or fixed effect model was utilized depending on the heterogeneity.Odds ratio(OR)and 95% confidence interval(95%CI)were used to evaluate the effect.The value of two-tailed P <0.05 represented a statistical significance.Begg and Egger′s tests were utilized to evaluate the publication bias.Meta-analysis was performed by Review Manager 5.3.2 and Stata 12.0.Results: 1.The outcomes of clinical data Overall analysis displayed that the rate of EGFR mutation was higher in >60 year-old,female,non-smoking and adenocarcinoma group(all P-value<0.05).EGFR subtype analysis showed that the rate of EGFR exon 19 mutation was higher in female,non-smoking and adenocarcinoma group(all P-value <0.05).The rate of EGFR exon 21 mutation was higher in >60 year-old,female,non-smoking,adenocarcinoma andⅠ to Ⅱgroup(all P-value<0.05).Overall and subgroup analyses demonstrated that regardless of the status of gender and smoking,the rate of EGFR mutation in carcino-embryonic antigen(CEA)negative group was lower than that in CEA positive group.The rate of anaplastic lymphoma kinase(ALK)rearrangement in ≤60 year-old group was higher than >60 year-old group,while no correlation between ROS-1 and age was observed.Additionally,the rate of ALK rearrangement and ROS-1 positive were not correlated with gender,smoking status,stage and pathological type(all P-value>0.05).They also were not related with tumor markers(CEA,carbonbydrate antigen125(CA125),carbonbydrate antigen199(CA199),neuron-specific enolase(NSE),pro-gastrin releasing peptide,(Pro-GRP),squamous cell carcinoma antigen(SCC-Ag)and cytokeratin 19 fragment(CYFRA21-1))(all P-value>0.05).Unconditional logistic regression analysis proved that CEA was a independent factor of EGFR status(OR=2.258,95CI%: 1.444-3.532,P<0.001).2.The outcomes of meta-analysis 27 studies incorporating 5084 cases were included in this meta-analysis.The result exhibited that the rate of EGFR mutation was higher in <60 year-old,female,non-smoking and adenocarcinoma group.The rate of EGFR mutation in CEA negative group was lower than CEA positive group(OR=0.43,95%CI: 0.34-0.55,P<0.00001),while the rate of EGFR mutation in SCC-Ag negative group was higher than that in SCC-Ag positive group(OR=2.51,95%CI: 1.70-3.72,P<0.00001).No correlation existed between EGFR mutation and CA125,CA199,NSE,Pro-GRP,CYFRA21-1(all P-value>0.05).Conclusions: 1.CEA was an independent factor of EGFR status,and patients with CEA positive harbored higher rate of EGFR mutation.2.No correlation was observed between CEA and ALK,ROS-1 status.EGFR,ALK and ROS-1 were not correlated with CA125,CA199,CYFRA21-1,SCC-Ag,NSE and Pro-GRP.3.Meta-analysis showed the rate of EGFR mutation was higher in CEA positive group and SCC-Ag negative group in Chinese NSCLC patients.