Correlation Between The Risk Of Lymph Node Metastasis And Common Driver Gene Mutations In Lung Adenocarcinoma

Objective:The reaearch is aiming to analyze the lymph node metastasis rate of lung adenocarcinoma with different gene mutations,and to determine which type of gene mutations is a high risk factor for lymph node metastasis,so as to closely monitor the disease progression of these postoperative patients with that gene mutation and develop potential treatments.Methods:1.Through the data management system of the Molecular Diagnosis Center of Yunnan Cancer Hospital,799 cases of pathological specimens of lung adenocarcinoma submitted for examination by the Second Department of Thoracic Surgery from January 2018 to December 2020 were retrieved.According to the criteria for case selection and exclusion,434 cases were selected,and then checked the medical records through the medical record retrieval system of Yunnan Cancer Hospital,and collected the clinical data of the included cases:including gender,age,hometown,smoking history,tumor location,tumor size,postoperative lymph node examination results(with lymph node matastasis or not).2.Collected and sort out various data,then made a Statistic analyze using SPSS 25.0 statistical software package.In the part I,the general clinical features of all cases(age,gender,hometown,smoking history,tumor location,tumor diameter)were analyzed as a single factor,and the characteristics related to lymph node metastasis of lung adenocarcinoma were obtained.Then these characteristics were included into Binary logistic regression analysis to screen out the risk factors for lymph node metastasis of lung adenocarcinoma.In the part II,all cases were divided into three categories according to the risk factors(tumor diameter)of lung adenocarcinoma lymph node metastasis obtained in the first part:T1(≤3cm),T2(>3cm and ≤5cm),T3(>5cm and ≤7cm).The correlation between gene mutation types and lymph node metastasis was analyzed,and the lymph node metastasis rate of different driver genes was obtained.Results:Among the 434 cases included,67 cases’ genetic tests revealed wild-type(15.44%),and 367 cases detected genetic mutations(84.56%),covering eight genotypes recommended by the guidelines.Most of the cases had no lymph node metastasis,and the cases with lymph node metastasis accounted for 16.59%(72 cases).1.A univariate analysis of the basic clinical characteristics of the lymph node metastasis group and the non-lymph node metastasis group showed that there is nocorrelation between the presence or absence of lymph node metastasis and age(t=0.965,P>0.05),gender(2=2.909,P>0.05),the location of tumor(2=4.672,P>0.05),Native place(2=0.641,P>0.05),while the difference of smoking history(2=4.710,P<0.05)and tumor diameter(2=51.214,P<0.05)between two groups with lymph node metastasis or not was statistically significant.The two factors,smoking history and tumor diameter,were further included in the binary logistics regression analysis.The results showed that although smoking history was related to lymph node metastasis,it wasn’t a dangerous factor for lymph node metastasis.Tumor diameter(OR=4.34,P<0.05)was a risk element influencing lymph node metastasis of lung adenocarcinoma.3.Classified by tumor diameter:T1 stage(≤3cm),T2 stage(>3cm and ≤5cm),T3 stage(>5cm and ≤7cm),and respectively analyzed the relationship between gene mutation type and lymph node metastasis,the results show as that:(1)The analysis of 347 cases of T1 stage(≤3cm)lung adenocarcinoma showed that the type of gene mutation was significantly correlated with lymph node metastasis(2=71.206,P<0.05).Except for the two genotypes of RET rearrangement and MET amplification without lymph node metastasis,the highest rate of lymph node metastasis in the all gene mutation types(lymph node metastasis rate of each gene mutation type=The number of lymph node metastases in this genotype/the total number of mutations in this genotype)is BRAF mutation(50.00%),followed by KRAS mutation(38.89%),whose lymph node metastasis rate was similar with ROS1 rearrangement(37.5%),followed by EGFR-L858R(11.11%)and HER2 mutation(10.00).%)and wild type(6.90%),EGFR-19del(2.82%),EGFR rare mutation(2.08%).(2)The analysis of 75 cases of T2 stage(>3cm and ≤5cm)lung adenocarcinoma showed that the type of gene mutation was significantly correlated with lymph node metastasis(P<0.05).By the comparison between the two groups of lung adenocarcinoma with lymph node metastasis or not,the lymph node metastasis rate in descending order is:BRAF mutation(87.50%)>ALK rearrangement(57.14%)>EGFR-L858R(38.89%)>EGFR rare mutation(27.27%)>EGFR-19del(20.00%)>Wild type(14.29%).In addition,lymph node metastasis was not found in RET rearrangement,MET amplification,ROS1 mutation and HER2 mutation in T2 stage cases,while the all 4 cases of KRAS mutation in T2 stage had lymph node metastasis.(3)In the comparison of 12 cases of lung adenocarcinoma of T3 stage(>5cm and≤7cm),the difference in gene mutation types between the two groups of lung adenocarcinoma with lymph node metastasis or not was not statistically significant(P>0.05).In the 12 cases of T3 stage lung adenocarcinoma included,HER2 mutation,RET rearrangement and MET amplification were not found,containing:l case of EGFR-19del,2 cases of EGFR-L858R,1 case of ALK rearrangement,l case of BRAF mutation,all existed lymph node metastasis.Lymph node metastasis was not found in one case of ROS1 mutation and one case of KRAS mutation.There was 1 case with lymph node metastasis in the 3 cases of EGFR rare mutation,and 1 cases with lymph node metastasiswith of 2 cases of wild type mutation.Conclusions:1.About 85%of primary lung adenocarcinoma cases detected gene mutations,especially EGFR mutations,accounting for about half.2.With the development of early surgical intervention of pulmonary nodules,most of the patients(about 83.41%)underwent radical resection of lung cancer had no lymph node metastasis.3.Tumor diameter is a risk factor for lymph node metastasis of lung adenocarcinoma.4.Patients with lung adenocarcinoma with different gene mutations have various tendency of lymph node metastasis.In the lung adenocarcinoma of T1-2 stages,compared with other mutations,there exists higher risk of lymphnode metastasis among patients with BRAF mutations,suggesting that for these patients,postoperative adjuvant treatment should be strengthened and serious recurrence monitoring shoud be performed.