title: EGFR mutation status in plasma and tumor tissues in non-small cell lung cancer serves as a predictor of response to EGFR-TKI treatment.
abstract: OBJECTIVE
  Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) can effectively control non-small cell lung cancer (NSCLC). Therefore, EGFR mutations should be detected before lung cancer patients undergo EGFR-TKI therapy. This study assessed the feasibility and predictive value of EGFR mutations in peripheral blood samples.
  
  
  METHODS
  EGFR mutations in exons 19 and 21 were analyzed in tumor tissue and plasma DNA samples from 121 NSCLC patients using amplification refractory mutation system (ARMS) and the integrated technique of mutant enriched PCR (me-PCR) and denaturing high performance liquid chromatography (DHPLC), respectively.
  
  
  RESULTS
  EGFR mutations were detected in 36.4% of tumor tissues and 34.7% of the plasma at a concordance rate of 85.1% (103/121). The sensitivity and specificity of plasma EGFR mutations were 77.3% and 89.6%, respectively. The gender and tumor histology of patients served as independent predictors of EGFR mutations in both tumor tissues and plasma, while CEA level was an independent predictor of EGFR mutations in the plasma. Furthermore, EGFR-TKI treatment showed a significantly higher objective response rate (ORR), median progression-free survival (mPFS), and overall survival (mOS) in patients harboring EGFR mutation than those that did not exhibit EGFR mutation (ORR: 69.4% versus 13.0% in tissues, P < 0.001; 64.5 % vs. 28.6% in the plasma, P = 0.006. mPFS: 10.4 months versus 4.1 months in tissues, P<0.001; 10.5 months vs. 5.2 months in the plasma, P=0.001. mOS: 25.7 months versus 8.3 months in tissues, P=0.005; 25.7 months vs. 13.5 months in the plasma, P=0.038).
  
  
  CONCLUSIONS
  EGFR mutations can be detected in the plasma using the integrated technique of me-PCR and DHPLC, which enables us to predict patient response to EGFR-TKI therapy. High serum CEA levels served as an independent predictor for plasma EGFR mutations.
authors.affiliation: a Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University , Chongqing , China.
authors.forename: Dan
authors.initials: D
authors.lastname: Que
authors.affiliation: a Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University , Chongqing , China.
authors.forename: He
authors.initials: H
authors.lastname: Xiao
authors.affiliation: b Beijing Epigenetics Biotechnology Co. Ltd. , Beijing , China.
authors.forename: Baojian
authors.initials: B
authors.lastname: Zhao
authors.affiliation: b Beijing Epigenetics Biotechnology Co. Ltd. , Beijing , China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: c Department of Pathology , Daping Hospital and Research Institute of Surgery, Third Military Medical University , Chongqing , China.
authors.forename: Qiushi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: c Department of Pathology , Daping Hospital and Research Institute of Surgery, Third Military Medical University , Chongqing , China.
authors.forename: Hualiang
authors.initials: H
authors.lastname: Xiao
authors.affiliation: a Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University , Chongqing , China.
authors.forename: Ge
authors.initials: G
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011237:Predictive Value of Tests; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: CEA; DHPLC; EGFR mutation; EGFR-TKI; NSCLC; survival; treatment response