BackgroundLung cancer has become the tumor with the highest morbidity and mortality in the world,and the 5-year survival rate is still low,so that the health care of people in my country even the world is still facing great challenges.With the further understanding of various molecular mechanisms of lung cancer and the disclosure of the results of various clinical trials,lung cancer has gradually changed from the traditional radiotherapy and chemotherapy model to the individualized precision treatment combining surgery,targeted therapy,immunotherapy and radiotherapy and chemotherapy mode.As one of the driving genes of lung cancer,MET gene has also received more attention.In recent years,more and more studies have been conducted on the mechanism of MET gene in tumors.However,there are many types of MET gene variants,which often makes clinicians full of worries and doubts.MET amplification is one of the altered forms of MET gene,which can not only serve as one of the drug resistance mechanisms of EGFR-TKI,but also appear in the form of primary amplification.There are few approved MET amplification inhibitors and the efficacy is not as good as EGFR,ALK and other inhibitors And at present,little is known about the difference of primary MET amplification among populations and its impact on the prognosis of lung cancer.ObjectiveThis study aims to analyze the clinicopathological features of patients with non-small cell lung cancer(NSCLC)and the effect of MET amplification on progression-free survival and prognosis of patients with advanced first-line chemotherapy in order to provide data reference for the research and development of targeted drugs and clinical treatment.MethodsFrom January 2016 to September 2018,the newly diagnosed patients with NSCLC and NGS testing diagnosed by pathology in the First Afiliated Hospital of Zhengzhou University were selected and the inclusion and exclusion criteria were strictly enforced.The clinical data of 537 subjects were studied retrospectively.According to whether MET was amplified or not,the patients were divided into MET amplification group and MET non-amplification group.The NGS test results and related clinical data were collected by electronic medical record and PACS system,such as sex,age,smoking history,tumor family history,pathological type,distant metastasis,TNM stage,PD-L1,PD-1,TTF-1 and treatment.Patients were followed up by telephone or outpatient clinic,and the deadline was January 31,2021.The data were statistically processed and analyzed by SPSS26.0,and the test standard was a=0.05.Results1.Among the 537 patients with NSCLC,there were 36 patients with MET amplification and 501 patients with non-amplification of MET.The co-mutation of MET with EGFR,ERBB2 and KRAS was found in 18 cases,3 cases and 2 cases,respectively.MET amplification combined with 2 or more gene co-mutations included:MET amplification+EGFR mutation+ERBB2 20 insertion mutation in 2 cases,MET amplification+ROS 40 exon missense mutation+KRAS copy number amplification in 1 case.2.Compared with those without MET amplification,MET amplification was more common in NSCLC patients with lymph node metastasis,adrenal metastasis,TNM stage for Ⅲ~Ⅳ,TTF-1 positive,PD-L1 positive,and PD-1 positive(P<0.05),while there was no significant difference in gender,age,smoking history,family history of tumor,pathological type,bone metastasis and brain metastasis.(P>0.05).3.The progression-free survival of patients with advanced MET-amplified lung adenocarcinoma who received first-line chemotherapy was shorter than that of lung adenocarcinoma patients without MET amplification,and the difference was statistically significant(P<0.05).The progression-free survival of patients with advanced MET-amplified lung squamous cell carcinoma who were received first-line chemotherapy was shorter than that of patients without MET amplification,but the difference was not statistically significant(P>0.05)4.For patients with lung adenocarcinoma who underwent radiotherapy and chemotherapy alone,the overall survival of those with MET amplification was shorter than that of those without MET amplification,and the difference was statistically significant(P<0.05).For patients with lung squamous cell carcinoma who underwent radiotherapy and chemotherapy alone,the overall survival of those with MET amplification was shorter than that of those without MET amplification,the difference was statistically significant(P<0.05).Conclusion1.Primary MET amplification can co-exist with EGFR,ERBB2 and other driving gene mutations and jointly mediate the occurrence and development of tumors.NGS detection will help us select the target drugs.2.Primary MET amplification mostly occurs in NSCLC patients with TNM stages for Ⅲ~Ⅳ,with lymph node metastasis,adrenal metastasis,and positive expression of TTF-1,PD-L1,and PD-1.3.Primary MET amplification in patients with advanced NSCLC may indicate a poor prognosis. |