Research On The Relationship Between Aberrant Status And Clinicopathological Characteristics Of Driving Genes In 1200 Patients With Non-small Cell Lung Cancer

Purpose In this research,we investigated the frequency of common driving genes of nonsmall cell lung cancer(NSCLC)and analyzed their association with clinicopathologic parameters in Shandong Peninsula.Methods 1.The pathological and medical records of 1200 patients with NSCLC diagnosed by the Affiliated Hospital of Qingdao University from 2016 to 2019 were collected,including 880 surgical resection specimens,200 biopsy specimens and 120 peripheral blood specimens.2.The status of 10 driving genes were evaluated by next-generation sequencing(NGS)in 1200 NSCLC specimens,including EGFR,ALK,ROS1,BRAF,HER2,PIK3 CA,KRAS,RET,MET and NRAS.3.The correlation between driving gene mutations and clinicopathologic characteristics were analyzed by statistical software SPSS 24.0.Results 1.In 1200 specimens,there were 659(54.9%)females and 541(45.1%)males.The average age was 60.7 years(range,22-97 years),the median age was 61.0 years.And 340(28.3%)patients were current or former smokers,860(71.7%)were nonsmokers.The pathological analysis identified that 1084(90.3%)cases were from adenocarcinoma,75(6.3%)cases were from squamous cell carcinoma,26(2.2%)cases were from adenosquamous carcinoma,9(0.7%)cases were from large cell neuroendocrine carcinoma,3(1.1%)cases were from NSCLC-NOS,1(0.1%)case was from carcinosarcoma,1(0.1%)case was from pleomorphic carcinoma and 1(0.1%)case was from lymphoepitheliomalike carcinoma.And,583(48.6%)patients were classified as stage I,132(11.0%)cases as stage II,265(22.1%)cases as stage III and 220(18.3%)cases as stage IV.2.Overall,903(75.3%)patients harbored at least one gene mutation in 1200 cases with NSCLC,853(71.1%)cases were single gene mutation,50(4.2%)cases were multi-gene mutations,297(24.8%)cases were no gene alteration.EGFR was the most common type of mutation(665,55.4%),followed by KRAS(133,11.1%),HER2(43,3.6%),PIK3CA(40,3.3%),ALK(30,2.5%),BRAF(18,1.5%),MET(10,0.8%),RET(7,0.6%),ROS1(6,0.5%)and NRAS(4,0.3%).The mutation types of 50 cases of multi-gene mutations were as follows,EGFR/PIK3CA(23 cases),EGFR/HER2(10 cases),KRAS/PIK3CA(3 cases),HER2/KRAS(3 cases),EGFR/KRAS(3 cases),BRAF/PIK3CA(2 cases),EGFR/MET(2 cases),EGFR/ROS1(1 case),EGFR/NRAS(1 case),KRAS/PIK3CA/HER2(1 case),EGFR/MET/HER2/KRAS(1 case).3.Gene mutation was associated with gender,age,smoking history,serum tumor marker concentration,histological type and clinical stage(P<0.05).EGFR mutation was associated with nonsmoker,normal level of serum tumor markers,women with adenocarcinoma in early stage(P<0.05),and no correlation with age and tumor location.The most common mutation sites of EGFR were 21 L858 R and 19 del.ALK rearrangement was more common in adenocarcinoma with mucus-producing component,micropapillary structure,airway dissemination and invasion the pleura of the lung(P<0.05).Mucus-producing component and micropapillary structure were associated with ROS1 rearrangement(P<0.05).The BRAF mutation was significantly associated with micropapillary structure and lymph node or organ metastasis in advanced patients(P<0.05).KRAS mutation tend to be detected in man,smokers and patients who had a higher level of serum tumor markers(P<0.05).KRAS mutation rate was also higher in tumor tissues containing mucus-producing component(P<0.05).The PIK3 CA mutation rate was higher in patients with lymph node or organ metastasis in advanced stage(P<0.05).HER2 alteration was associated with the younger patients(P<0.05).Conclusion Overall,75.3% of patients had gene mutation and 8.5% of patients harbored synchronous mutation or multisite mutation.Most patients can get benefit from targeted therapy.Gene mutation was significantly associated with clinicopathological characteristics.EGFR and KRAS mutations were associated with gender,age,smoking history,serum tumor marker concentration,histological type,and clinical stage.There was a correlation between BRAF and PIK3 CA mutations in lymph node or organ metastasis and clinical stage.ALK and ROS1 were associated with growth patterns in histological type of tumor tissue.There was a correlation between HER2 mutation and age.Clinicians can select suitable detection population and target genes depending on clinicopathological characteristics for combined detection of multiple driving genes,aimed to avoid missed detection and large-scale excessive detection.