Detection Of The Driver Oncogenes In Lung Adenocarcinoma By NGS And The Correlation Between EGFR Gene Mutation And Serum Tumor Markers

Objectives:To analyze the driver oncogenes in lung adenocarcinoma by next-generation sequencing and the correlation between EGFR gene mutations and serum tumor markers of newly diagnosed lung adenocarcinoma.Methods:A retrospective study of 77 patients with primary lung adenocarcinoma who were admitted to the Department of Respiratory Medicine,Bethune First Hospital,Jilin University from June 2017 to December 2018 was conducted.57 patients had not received any anti-tumor treatment including surgery,radiotherapy,chemotherapy,targeted therapy or other anti-tumor therapy etc.20 patients were retreated patients who had received or were receiving anti-tumor therapy.The 9 driver oncogenes of 77 patients including EGFR、KRAS、HER2、MET、ALK、RET、BRAF、ROS1 and PIK3 CA were detected by NGS.The specimens were pathologically diagnosed as primary lung adenocarcinoma.The results of blood tumor markers consisting of CEA,CA199,CA125,CA242 and NSE were detected for the first time of 57 original treated patients with primary lung adenocarcinoma.Results:1、There are 77 patients with lung adenocarcinoma,that 75.32%(58/77)of them were detected to own the driver oncogenes,and 20.78%(16/77)were detected to have two or more driver oncogenes.Among the single gene mutations,the detection rate of EGFR,KRAS,HER2,MET,ALK,and RET genes was 37.66%,7.79%,3.90%,2.60%,1.30%,and 1.30%,respectively.Among the double gene mutations,the detection rate of EGFR with MET gene was 6.49%(5/77),which is the highest value.The 1.30%(1/77)of patients with three driver oncogenes(KRAS,MET,PIK3CA)were detected.The total EGFR gene mutation rate was 46.75%(36/77),where two or more EGFR gene mutation types or EGFR gene amplification were detected in 15.58%(12/77)patients.Among the single mutation types of EGFR,Exon19 del and Exon21 L858 R had the highest mutation rate,both of the value are 27.78%(10/36).2、Among the 57 patients with newly diagnosed lung adenocarcinoma,there was no significant difference in age,gender,smoking history,and clinical stage between EGFR mutant patients and EGFR wild-type patients.The EGFR mutation rate in initial treated lung adenocarcinoma patients of CEA ≥5 ng/ml was higher than that in the CEA normal group(CEA<5 ng/ml)(55.56% vs 28.57%,P=0.048).The EGFR mutation rate in initial treated lung adenocarcinoma patients of the normal group of blood CA199(CA199<37 U/ml)was higher than that in the CA199 abnormal group(CA199≥37 U/ml)(55.26% vs 26.32%,P=0.039).Multivariate logistic regression analysis showed that patients with CEA≥5 ng/ml had a 3.5-fold increased likelihood of EGFR gene mutations in patients with CEA<5 ng/ml.The rate of patients to have EGFR gene mutations with CA199≥37 U/ml decreased about 80% than patients with CA199<37 U/ml.Conclusions:1.The driver oncogenes in tumor tissues of lung adenocarcinoma can be comprehensively and accurately detected by NGS.2.The mutation rate of EGFR gene is related to the expression level of serum tumor markers in newly diagnosed lung adenocarcinoma.Patients with lung adenocarcinoma with serum CEA≥5 ng/ml or CA199<37 U/ml are supposed to have a higher EGFR gene mutation.