Relationship Between Positive Driving Gene And Clinical Characteristics In Non-small Cell Lung Cancer

Objective: The arrival of the era of precision medicine has greatly promoted the individualized targeted therapy of lung cancer.The premise of targeted therapy is to clarify the specific conditions of the target gene,so as to guide clinical treatment.The purpose of this study is to explore the mutation characteristics,demographic characteristics and oncology characteristics of each gene of non-small cell lung cancer,and to analyze the correlation between multi-gene coexistence and multiple metastasis,so as to better guide clinical individualized diagnosis and treatment.Methods: Patients with non-small cell lung cancer who received diagnosis and treatment in the Affiliated Hospital of Guilin Medical University from January 2018 to December 2021,and patients who underwent routine detection of driver genes(EGFR,KRAS,ALK,ERBB2,BRAF,ROS-1,MET,RET,NTRK)by next-generation sequencing method before treatment were selected.Collect general clinical data(such as name,sex,age,nationality,smoking history)and imaging data(such as tumor maximum diameter,location,pathological type,clinical stage,lymph node metastasis,distant metastasis).Results:(1)A total of 290 patients with non-small cell lung cancer were included in this study,and the mutation rates of each gene were as follows:EGFR 45.52%(132/290),KRAS 10.34%(30/290),ALK 7.59%(22/290),ERBB2 5.17%(15/290),BRAF 4.14%(12/290),ROS-1 3.10%(9/290),MET4.83%(14/290),and RET 2.07%(6/290).NTRK gene detection was completed in 177 patients,and the mutation rate was 2.82%(NTRK1 1.69%(3/177),NTRK3 1.13%(2/177)).(2)The most common mutation type of EGFR gene is the missense mutation of L858 R in exon 21.In this study,there was a rare mutation of EGFR-KDD gene.Univariate analysis showed that there was significant correlation between EGFR gene mutation and sex,smoking history,pathological type,clinical stage and distant metastasis(P<0.05).Multivariate analysis showed that EGFR gene mutation was associated with smoking history,pathological type and clinical stage(P<0.05),while EGFR gene mutation was not correlated with sex and age(P>0.05).(3)The most common mutation type of KRAS gene is exon 2 G12 C missense mutations.KRAS gene can coexist with EGFR,ALK,ROS-1,MET and RET.The mutation status is significantly correlated with sex and smoking status(P<0.05),but no significant correlation with age(P>0.05).(4)The main mutation type of ALK gene is EML4-ALK gene fusion,accounting for 81.82%(18/22).When ALK gene participates in multi-gene coexisting mutation,it mainly exists in the form of point mutation,and the correlation analysis between ALK gene mutation status and age is statistically significant(P < 0.05).(5)The most common mutation types of ERBB2 gene are exon 20 Y772＿A775dup(3/15,20.00%)and gene amplification(3/15,20.00%).ERBB2 gene often coexists with EGFR gene.(6)The most common mutation type of BRAF gene is exon 15 V600 E missense mutationin.Among them,6 cases had coexisting mutation of BRAF gene,all of which occurred at the same time as EGFR gene.(7)The most common ROS-1gene is ERZ-ROS1 gene fusion(3/9,33.33%).One case of ROS1-SCNN1 D gene fusion has not been reported in previous studies.ROS-1 gene involved in the coexistence of multiple gene mutations mainly exists in the form of point mutations.(8)The most common mutation type of MET gene is gene amplification,and we found 2 cases of MET exon 14 skipping mutation.About71.43%(10/14)of MET gene mutation appeared in coexisting mutation,and most of them had simultaneous mutation with EGFR gene.(9)Among the coexisting gene mutations,the RET gene existed as a point mutation type,while the RET fusion type did not coexist with other genes.(10)EGFR and KRAS,ALK,ERBB2,BRAF,ROS-1,MET,RET,NTKR can coexist mutations.(11)There was a significant correlation between EGFR gene and KRAS,ALK gene(P<0.05),and a negative correlation.(12)The probability of brain metastasis and bone metastasis in EGFR gene positive group was higher than that in EGFR gene negative group(P<0.05).Conclusions:(1)EGFR gene mutations are more common in non-smoking and adenocarcinoma patients,and EGFR gene mutations may be more prone to brain and bone metastasis.(2)KRAS gene mutations are more common in male patients who smoke,but have nothing to do with age and pathological type.(3)ALK gene mutations are more common in patients less than 60 years old,but have nothing to do with sex,smoking history and pathological types.(4)Coexisting gene mutations mostly occur between point mutation types,and fusion types generally do not participate in coexisting mutations.