The Clinical Research Of The Correlation Between The Expressive Level Of Epidermal Growth Factor Receptor Gene Sensitive Mutation With Non-small Ceil Lung Cancer

Background and purpose:Today lung cancer is the first tumor in the world,and about17%ofnew cancer cases is lung cancer every year, and about23%of cancerpatients died of lung cancer.Epidermal growth factor receptor (EGFR) isa driver gene and has a relationship with the development andprogression of lung cancer. EGFR tyrosine kinase somatic mutations arecommon in non-small cell lung cancer, especially women, Asian people,non-smoking and adenocarcinoma patients.Many studies have confirmedthat EGFR mutations for targeted therapy has a positive role in predicting,about75%of the patients used tyrosine kinase inhibitors have betterresponse rate,but nothing in no mutation. However, the non-smal celllung cancer have heterogeneity. The proportion of EGFR sensitive mutantcells in patients will effect the reaction of EGFR-TKI.The molecularanalysis have found that EGFR gene copy number occurred about10%to40%in non-small cell lung cancer, Cappuzzo F et al suggest theexpression level of EGFR gene sensitive mutation may have the same orbetter lifetime prediction effect than EGFR mutation, but the role of theexpression level of EGFR gene sensitive mutation in clinical application are still controversy.The relationgship between the expression level ofEGFR gene sensitive mutation with the clinical features and prognosis ofnon-small cell lung cancer need more clinical trials. This studyretrospectively analyzes63cases of non-small cell lung cancer from theChina-Japanese hospital oncology clinical center.Methods:In this study,the information of63patients of non-small cell lungcancer from July2013to March2014China-Japanese hospital oncologyclinical center was statistically analysed,and these patients detected theexpression level of EGFR gene sensitive mutation by ARMS(Sampleswere collected from postoperative specimens,biopsy tissue,not includingexfoliated cells). The pathologic type is adenocarcinoma. The presence ofEGFR gene mutations (including sensitive mutation in exon19E746-A750and L858R,L861Q in exon21).According to the number of cycles (Ct,the number of cycles when the fluorescence signal of each reactiontube to reach the threshold) parameters of ARMS to detect the level ofEGFR gene sensitive mutation.We get the informati on through thehospitalized case and telephone follow-up. Using t test,chi square test tocompare the correlation between the clinical features of non-small–celllung cancer with EGFR gene sensitive mutation expression level.Clinicalapplication of EGFR-TKIs as first-line therapy for2months and using RECIST standard evaluate the affects,following up every4weeks,medianfollowup time is16months.Draw survival curve Kaplan-Meier.Results:1．The basic clinical data: A total of63cases of patients, thepathologic type is adenocarcinoma, and the mutation of EGFR gene exon19in27cases of mutations, exon21mutation in36cases;male23cases,female40cases.Age from30to84, the median age is60years old.22cases are smokers,41cases were nonsmokers(Previous smoked fewerthan100cigarettes in their life time); Low differentiation40cases,intermediate differentiation18cases, high differentiation5cases; Clinicalstage ofⅠ13cases,Ⅱ4cases, Ⅱ10cases, Ⅱ36cases;No lymph nodemetastasis15cases,lymph node metastasis38cases (Ipsilateral bronchial/hilar lymph node metastasis14cases, ipsilateral mediastinal/subcarinallymph node metastasis15cases, mediastinal, hilar contralateral, ipsilateralor lateral supraclavicular lymph node metastatic19cases);Withoutdistant metastases28cases, distant metastasis35cases(brain metastasis15cases,bone metastasis10cases,liver metastasis3cases,multiplemetastases7cases).2. Comparison of he clinical features:Low expression group includes38cases, male16cases, female22cases.The maximum is80years old,minimum is30years, the median age is59years old.17cases aresmokers,21cases were nonsmokers;Low differentiation11cases, intermediate differentiation11ases, high differentiation4cases; Clinicalstage ofⅠ11cases, Ⅱ2cases, Ⅱ8cases, Ⅱ17cases; The tumor sizeof T112cases, T214cases, T36cases, T46cases;No lymph nodemetastasis12cases, lymph node metastasis16cases with;Without distantmetastases20cases, distant metastasis18cases.High expression group includes25cases, male7cases, female18cases.The maximum is84years old, minimum is39years, the medianage is57years old.5cases are smokers,20cases were nonsmokers;Lowdifferentiation17cases, intermediate differentiation7cases, highdifferentiation1cases; Clinical stage ofⅠ2cases, Ⅱ2cases, Ⅱ2cases,Ⅱ19cases; The tumor size of T15cases, T29cases, T38cases, T43cases;No lymph node metastasis3cases, lymph node metastasis22caseswith;Without distant metastases8cases, distant metastasis17cases.There is statistical differences between EGFR gene sensitivemutation expression level with smoking and TNM stage, The smokingand IV patients in high expression level group are more than lowexpression level group.But we can’t find the differences in age, gender,degree of differentiation, tumor size, lymph node and distant metastasis.3.The objective efficacy analysis:Low expression group: a total of38cases, after applying EGFR-TKItwo months,achieved complete remission (CR)0cases (0%),and partialresponse (PR)8cases (8/38,21%), stable disease (SD)20cases (20/38,53%), progressive disease (PD)10cases (10/38,26%). Objectiveresponse rate (ORR)(CR+PR) was21%(8/38), disease control rates(DCR)(CR+PR+SD) was74%(28/38).High expression group: a total of25cases, after applyingEGFR-TKI two months,achieved complete remission (CR)0cases(0%),partial response (PR)15cases (15/25,60%), stable disease (SD)10cases (10/25,40%), disease progression (PD)0cases (0%). Objectiveresponse rate (ORR)(CR+PR) was60%(15/25), disease control rates(DCR)(CR+PR+SD) was100%(25/25).The objective response rate and disease control rate in highexpression group were higher than lower expression group,ORR was60%and21%,P=0.002,DCR were100%and74%, P=0.005.4.Survival condition:Low expression group:a total of38patients,19cases of1-yearsurvival,of which9cases no disease progression.High expression group:atotal of25patients,19cases of1-year survival，of which12cases nodisease progression.Compared two groups of1year PFS%and1yearOS%,1year PFS%respectively48%and24%,P=0.045;1year OS%respectively76%and50%,P=0.0139. Median PFS10.5m vs7.0m.Conclusion:1. The non-smoker in high expression group are more than lowexpression group. 2. The phase IV patients in high expression group are more than lowexpression group.3. The sensitivity of EGFR gene mutation expression levels can beused as predictors of EGFR-TKI drug efficacy and survival time.