Analysis Of The Correlation Between EGFR Gene Mutation And Main Pathological Types And TTF-1 Expression In Lung Adenocarcinoma

BackgroundLung cancer is the leading cause of cancer death in the world,and lung adenocarcinoma is one of the common types of lung cancer.Adenocarcinoma had significant molecular heterogeneity.With the development of precision medicine,there were more and more studied on targeted treatment of lung adenocarcinoma.The activation of epidermal growth factor receptor(EGFR)pathway provided the possibility of treatment with tyrosine kinase inhibitors.The study on the relationship between pathological classification of lung adenocarcinoma and EGFR mutation had also attracted much attention,some studies had suggested that the mutation rate of EGFR gene in patients with acinar lung adenocarcinoma was high.Other studies had suggested that EGFR mutations were more common in lepidic predominant lung adenocarcinoma.However,there were few foreign studies on the pathological classification and EGFR gene mutation of lung adenocarcinoma.Thyroid transcription factor-1(TTF-1)was an important biomarker of lung adenocarcinoma with a specificity of 100%and a sensitivity of 94.6%.Foreign studies had shown that epidermal growth factor receptor was a downstream factor in TTF-1 amplified non-small cell lung cancer,In cells with EGFR gene mutation,the expression of TTF-1 could regulate the stability of EGFR pathway.Some studies had shown that TTF-1 expression and EGFR mutation were closely related to female,non-smoking status and adenocarcinoma.Some studies had shown that the expression of TTF-1 may predict EGFR mutation.There were few studies on the relationship between different pathological types of lung adenocarcinoma,TTF-1 expression and EGFR gene mutation,which needed to be further studied.ObjectiveTo explore the correlation between EGFR gene mutation and main pathological types,TTF-1 expression in lung adenocarcinoma.MethodsCollected 194 patients with primary invasive lung adenocarcinoma diagnosed by surgery and pathology in the First Affiliated Hospital of Zhengzhou University from January 2017 to January 2019 for retrospective study,divided the patients into EGFR mutation group and wild-type group according to the results of EGFR gene detection,divided the patients into TTF-1 positive group and TTF-1 negative group according to the expression level of TTF-1,recorded the patients' gender,age,smoking history,serum tumor markers,pathological diagnosis,main pathological types of lung adenocarcinoma,degree of differentiation,TNM stage,lymph node metastasis and other clinicopathological characteristics by electronic medical.record system.The results of EGFR gene mutation,TTF-1 expression and sex,age,smoking history,serum tumor markers,main pathological types,degree of differentiation,TNM stage and lymph node metastasis were all tested by ?2 test to screen out the influencing factors with statistical significance for EGFR gene mutation,and multivariate binary logistic regression analysis was used to analyze the factors influencing the results of EGFR mutation,and P<0.05 was statistically significant.Results1.A total of 194 patients with primary lung adenocarcinoma diagnosed by surgical resection and pathology were included,they were divided into a mutation group(120 cases)and a wild group(74 cases)based on the EGFR mutation results.The mutation group included mutations in exons 18,19,20 and 21,and the mutation rate of EGFR gene was 61.9%(120/194).The mutation rate of EGFR gene in women was higher than that in men(72.4%vs 49.4%).The mutation rate of EGFR gene in patients aged? 60 years old was higher than that in patients under 60 years old(69.1%vs 55.0%).The mutation rate of EGFR gene in non-smoking patients was higher than that in smoking patients(68.5%vs 43.1%),and the difference was statistically significant(all P<0.05).There was no significant difference in EGFR gene mutation between CEA positive and negative patients(P>0 05).2.In the main pathological classification of lung adenocarcinoma,the mutation rate of EGFR gene in acinar adenocarcinoma was higher than that in non-acinar adenocarcinoma(68.5%vs 50.0%,P<0.05),the mutation rate of EGFR gene in non-solid adenocarcinoma was higher than that in solid adenocarcinoma(67.3%vs 34.4%,P<0.05).There were significant differences in EGFR gene mutation among patients with low differentiation,medium-low differentiation,middle differentiation,high-medium differentiation and high differentiation(27.6%vs 64.2%vs 68.6%vs 83.3%vs 75.0%,P<0.05).The mutation rate of EGFR gene in patients without lymph node metastasis was higher than that in patients with lymph node metastasis(67.7%vs 50.7%,P<0.05).Among the EGFR mutants,there were 107 cases with positive mutations in exon 19 or exon 21,the mutation rate of exon 19 or 21 in acinar adenocarcinoma and non-solid adenocarcinoma was higher than that in non-acinar adenocarcinoma and solid adenocarcinoma,respectively(60.5%vs 45.7%,59.9%vs 31.3%,P<0.05).3.According to the results of TTF-1 detection,185 cases in the positive group and 9 cases in the negative group.There was no significant difference in the positive expression of TTF-1 between male and female,age? 60 years old and<60 years old,smoking history and non-smoking history,CEA positive expression and negative expression,each major pathological type,each degree of differentiation,lymph node metastasis and no lymph node metastasis(all P>0 05).4.The EGFR gene mutation rate in TTF-1 positive patients was 64.3%(119/185),and the EGFR gene mutation rate in TTF-1 negative patients was 11.1%(1/9),the EGFR gene mutation rate in TTF-1 positive patients was significantly higher than that in TTF-1 negative patients,and the difference was statistically significant.Exons 19 and 21 were higher in EGFR gene mutation group,and the mutation rate of exon 19 or 21 in TTF-1 positive patients was significantly higher than that in TTF-1 negative patients,and the difference was statistically significant(57.3%vs 11.1%,P<0.05).5.The results of EGFR gene mutation in patients with lung adenocarcinoma were set as dependent variables,and the factors of significance for EGFR mutations were set as independent variables for multivariate binary Logistic regression analysis.The results showed that the independent influencing factors of EGFR gene mutation were gender(female vs male,OR=2.552,P<0.05),main pathological classification(acinar type vs solid type,OR=3.647,P<0.05;papillary type vs solid type,OR=7.010,P<0.05)and TTF-1 expression level(positive vs negative,OR=10.343,P<0.05).Conclusions1.Among the main pathological types of lung adenocarcinoma,EGFR gene mutations may be more common in acinar and papillary lung adenocarcinomas than in solid lung adenocarcinomas.2.TTF-1 may be related to the mutation of EGFR gene,and the patients with positive expression of TTF-1 may be more likely to carry the mutation of EGFR gene.