Relationship Between EGFR Gene Mutation And Serum Proteomic Expression In Non-small Cell Lung Cancer

Objects: To investigate the relationship between EGFR gene mutation and serum proteomic expression in non-small cell lung cancer(NSCLC) to screen the differential expressive proteins between EGRF gene mutation type NSCLC and wild type NSCLC,that we can gain help to predict the sensitivity of tyrosine kinase inhibitor(TKI) in NSCLC.Methods: 49 cases NSCLC patients were detected by Denaturing High Performance Liquid Chromatography(DHPLC) to analyze EGFR gene mutation. And the surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS) was applied to detect serum protein pattern with weak cation chips to analyze the differential expressive proteins between EGRF gene mutation type NSCLC and wild type NSCLC.Results:â‘ EGFR gene mutation was identified from 13 of 49 cases(19 exon deletion mutations in 10 cases,accounting for 76.92%;21 exon alternative mutation in 3 cases,accounting for 23.10%). Detection sensitivity was 100%.â‘¡With weak cation chips to detect these 49 NSCLC patients'serum proteingram before the surgery and 10 days after the surgery, we discovered:In preoperative serum samples , protein peak of 4597Da molecular weight was Significantly higher in NSCLC patients with EGFR gene mutation group(19 exon mutation and 21 exon mutation) than in those with EGFR gene wild group (P<0.05), with the sensitivity 76.92% and specificity 75%.Protein peak of 4597Da molecular weight was Significantly higher in NSCLC patients with EGFR gene 19 exon mutation type than in those with EGFR gene wild type (P<0.05), with the sensitivity 80% and specificity 75%.Protein peaks of 4597Da and 8694Da molecular weight were Significantly higher in NSCLC patients with EGFR gene 21 exon mutation type than in those with EGFR gene wild type (P<0.05).The sensitivity for distinguishing mutation was 66.67% and 100% respectively and the specificity was 75% and 72.22% respectively. Peak differences were also found in the postoperative serum samples, with the same sensitivity and specificity as above.To analyze the NSCLC patients'serum proteingram before and 10 days after the radical lung cancer operation by Biomarker Wizard and SPSS statistical software, we discovered that NSCLC patients'postoperative serum proteingram is lower than preoperative serum proteingram at the protein peaks of 3812Da,4791Da,6189Da,6430Da molecular weights(P<0.05), but higher at the 16080Da,16138Da(P<0.05),while these protein peaks'variance was no statistical difference between NSCLC patients with EGFR gene mutation group and those with EGFR wild group (P>0.05).Conclusion: DHPLC is a new and high-throughput technology to screen DNA sequence variation. It can screen EGFR gene mutations fast and accurately. Significantly different protein peaks were identified in sera between NSCLC patients with EGFR gene mutations and those with EGFR gene wild type.It is expected to screen the differential expressive proteins between the EGFR gene mutation type NSCLC and wild type NSCLC patients with application of totally new proteomics technology platform ------ SELDI-TOF-MS ,that help us to predict the sensitivity of tyrosine kinase inhibitor(TKI) and choose suitable patients accepting TKI therapy in NSCLC.