The Detection Of EGFR Mutation And Copy Number In The Serum Free DNA Of Advanced Nonsmall-cell Lung Cancer Patients And Its Clinical Significance

Objective:To approach the clinical significance of the detection of EGFR mutation and copy number in the circulating cell free DNA of advance nonsmall-cell lung cancer(NSCLC)patients,and studied the connection between EGFR mutation and copy number with the clinical pathology character of NSCLC and response to EGFR-TKI.Methods: From the February.2008 to the November.2009, We collected the blood serum of 65 patients with stageⅢB or stageⅣNSCLC and 10 healthy volunteer randomly. The quantity of serum was 1ml every person. And then we made the use of the real time fluorescent quantitation PCR to detect EGFR copy number in the Serum free DNA and detect the epidermal growth factor receptor mutations by mutant-enriched PCR .Finally,We assayanalyzed the relationship between the EGFR gene condition and the clinical pathology character and the response to EGFR-TKI in patients.Result:1. Among the advanced NSCLC patients,the average value of EGFR copy number was 61846657 copies/ml. In the healthy volunteer group, the average value was 3749263.8 copies/ml.In the group of NSCLC:the EGFR copy number of female patients was higher than male patients; the adenocarcinoma patients'copy number was the highest in three pathology types of NSCLC; The EGFR copy number of patients with smoking history was higher than never smoking patients.Moreover, The EGFR copy number of patients with EGFR mutation was higher than patients with EGFR widetype.However,the copy number of patients with stageⅢB or stageⅣNSCLC,response to or not response to Gefitinib and age<60 or age≥60 were not different in statistics analysis(P>0.05).2. The EGFR mutation rate of advanced NSCLC patients: patients with adenocarcinoma was higher than patients with the other pathology types of NSCLC; patients with smoking history patients was higher than never smoking patients. However, The EGFR mutation rate of patients between gender,stageⅢB or stageⅣand age<60 or age≥60 were not different in statistics analysis(P>0.05).3. The response rate of gefitinib of advanced NSCLC patients: patients with adenocarcinoma was higher than patients with the other pathology types of NSCLC; patients with smoking history was higher than never smoking patients; patients with EGFR mutation was higher than patients with EGFR widetype; However, The response rate of gefitinib of patients between gender,stageⅢB or stageⅣand age<60 or age≥60 were not different in statistics analysis(P>0.05).Conclusion:1.Making the use of the real time fluorescent quantitation PCR to detect the copy number of EGFR in the cell free DNA was effectual and feasible.And the copy number of EGFR in advanced NSCLC patient is higher than healthy volunteer.In the group of NSCLC,the EGFR copy number of female patients was higher than male patients; the adenocarcinoma patients'copy number was the highest in three pathology types of NSCLC; The EGFR copy number of patients with smoking history was higher than never smoking patients.Moreover, The EGFR copy number of patients with EGFR mutation was higher than patients with EGFR widetype.2. Detecting the epidermal growth factor receptor mutations by mutant-enriched PCR in the cell free DNA was effectual and feasible.The EGFR mutation rate of advanced NSCLC patients: patients with adenocarcinoma was higher than patients with the other pathology types of NSCLC; patients with smoking history patients was higher than never smoking patients.3.The response rate of gefitinib of advanced NSCLC patients: patients with adenocarcinoma was higher than patients with the other pathology types of NSCLC; patients with smoking history was higher than never smoking patients; patients with EGFR mutation was higher than patients EGFR widetype.4.Cell Free DNA in the blood serum of EGFR gene copy number would be used to detect and monitor the condition of micrometastasis of malignant tumor.But big sample will need to confirm this conclusion.5.Cell free DNA in the blood of EGFR mutation is closely relate to the response to gefitinib ,it may be an important reference of the targeted therapy of advanced NSCLC patients.