| Objective: To detect epidermal growth factor receptor(EGFR) gene mutation of NSCLC(non-small cell lung cancer, NSCLC) patients, combined with serum CEA, SCCAg levels were measured to assess EGFR gene mutation in peripheral blood and tumor marker levels were correlation targeted drug therapy.Methods: Collection of 46 cases from June 2014 to December 2015, NSCLC patients hospitalized Fourth Hospital of Hebei Medical University, Department of Respiratory Medicine. Application amplification refractory mutation system(amplification refractory mutation system, ARMS) to detect peripheral blood and paraffin-embedded tumor tissue EGFR gene mutation, serum CEA, SCCAg level was measured by electrochemical luminescence, and using SPSS17.0 software for statistical analysis.Results:1 Detecting EGFR gene in 46 cases of NSCLC patients using serum sample, EGFR gene mutation detection rate was 30.4%(14/46). In EGFR gene mutation cases, exon 21 missense mutation(L858R) 6 cases, the mutation rate was 42.9%(6/14), exon 19 deletions(19Del) 7 cases, the mutation rate was 50%(7/14), and 1 case was T790 M mutation in exon 20, mutation rate was 0.07%(1/14). Using paraffin tissue samples tested EGFR gene mutation detection rate was 47.8%(22/46). In these 22 cases, exon 21 missense mutation(L858R) 10 cases, the mutation rate was 45.5%(10/22), 19 outer exon deletion(19Del) 12 cases, the mutation rate was 54.5%(12/22), 1 case of co-mutation in exons 19, 20, and mutation type was mutation T790 M, mutation rate was 0.05%. The coincidence rate of EGFR gene mutation in serum samples with the corresponding tissue samples was 82.6%(38/46), and the Kappa value was 0.646(0.4<Kappa<0.7, u=7.189) by using the consistency of Kappa.2 Relationship between serum EGFR mutations and clinical characterristics of patients. In 46 patients, 22 males mutation was 13.6%(3/22) and 24 females mutation was 45.8%(11/24), mutation rate in female patients was significantly higher than that in male patients(P=0.018). Non-smokers 26 cases, the mutation rate was 42.3%(11/26), and 20 cases of smokers, the mutation rate was 15%(3/20), non-smokers mutation rate was significantly higher than smokers(P=0.046). 30 patients of adenocarcinoma, the mutation rate was 40%(12/30), 16 case of non-adenocarcinoma, the mutation rate was 12.5%(2/16)(P=0.092), no significant differences between these two groups. In addition, serum EGFR mutation with age and clinical staging of patients was no significant correlation;3 Relationship between serum tumor markers level and EGFR-TKI efficacy. After the gefitinib therapy, CEA levels increased mutation group, the patient’s CEA PFS was significantly higher than the normal group, the difference was statistically significant(10.8 and 6.8 months, P=0.000). However,after the gefitinib therapy, SCCAg elevated concentrations of the normal group was no statistically significant with prognosis group(10.4 and 7.1 months, P=0.401);4 Relationship between EGFR mutation and EGFR-TKI efficacy in peripheral blood. In 26 patients of receiving EGFR-TKI therapy, serum EGFR mutation-positive patients was 14 cases, who taking gefitinib after complete remission(CR) 1 cases, partial remission(PR) 8 patients had stable disease(SD) 2 cases progressive disease(PD) 3 cases, objective response rate of 64.3%(9/14), disease control rate was 78.6%(11/14). EGFR gene unmutated 12 patients taking gefitinib after complete remission(CR) 0 patients and partial remission(PR) 3 patients had stable disease(SD) 1 cases of progressive disease(PD) 8 cases, objective response rate 25%(3/12), disease control rate was 33.3%(4/12). After imatinib, EGFR mutations in patients compere with objective response rate and disease control rate was signifycantly higher than those taking gefitinib EGFR gene unmutated patients(P=0.045, P=0.02). EGFR mutations Median PFS was significantly higher in patients with non-mutated patients(11.4 and 6.8 months, P=0.001);5 CEA combined with EGFR mutation detection showed elevated levels of CEA and/or EGFR mutation-positive patients were better prognosis compared with the normal CEA levels and EGFR unmutated patients.(12.6 months and 10.4 months, 6.7 months, P=0.000). The difference was statistically significant. SCCAg combined with EGFR mutation detection can indication that after EGFR-TKI treatment, SCCAg normal levels and / or EGFR mutation-positive patients prognosis better than SCCAg elevated levels and EGFR unmutated patients(11.8 months, 8.3 months, 6.8 months, P=0.004).Conclusion:Detection EGFR mutations of NSCLC patients, the tissue samples from patients were not easy to obtain, the serum samples in peripheral blood can instead of tissue sample to detect EGFR gene mutation, selection patients of TKIs target therapy, and suggesting that EGFR gene mutations in peripheral blood can provide a reference for predicting NSCLC patients with EGFR-TKIs treatment efficacy. Combined detection of EGFR gene mutation in peripheral blood and serum levels of tumor markers can be advantageous predict EGFR-TKI treatment. |
PDF Full Text Request