title: Predictive value of K-ras and PIK3CA in non-small cell lung cancer patients treated with EGFR-TKIs: a systemic review and meta-analysis.
abstract: OBJECTIVE
  A meta-analysis was performed to augment the insufficient data on the impact of mutative EGFR downstream phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways on the clinical efficiency of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment of non-small cell lung cancer (NSCLC) patients.
  
  
  METHODS
  Network databases were explored in April, 2015. Papers that investigated the clinical outcomes of NSCLC patients treated with EGFR-TKIs according to the status of K-ras and/or PIK3CA gene mutation were included. A quantitative meta-analysis was conducted using standard statistical methods. Odds ratios (ORs) for objective response rate (ORR) and hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) were calculated.
  
  
  RESULTS
  Mutation in K-ras significantly predicted poor ORR [OR =0.22; 95% confidence interval (CI), 0.13-0.35], shorter PFS (HR =1.56; 95% CI, 1.27-1.92), and shorter OS (HR =1.59; 95% CI, 1.33-1.91) in NSCLC patients treated with EGFR-TKIs. Mutant PIK3CA significantly predicted shorter OS (HR =1.83; 95% CI, 1.05-3.20), showed poor ORR (OR =0.70; 95% CI, 0.22-2.18), and shorter PFS (HR =1.79; 95% CI, 0.91-3.53) in NSCLC patients treated with EGFR-TKIs.
  
  
  CONCLUSIONS
  K-ras mutation adversely affected the clinical response and survival of NSCLC patients treated with EGFR-TKIs. PIK3CA mutation showed similar trends. In addition to EGFR, adding K-ras and PIK3CA as routine gene biomarkers in clinical genetic analysis is valuable to optimize the effectiveness of EGFR-TKI regimens and identify optimal patients who will benefit from EGFR-TKI treatment.
authors.affiliation: 1 Department of Immunology, 2 Cancer Molecular Diagnostic Core Laboratory, 3 Biotherapy Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Immunology and Biotherapy, Tianjin 300060, China.
authors.forename: Jie-Ying
authors.initials: JY
authors.lastname: Chen
authors.affiliation: 1 Department of Immunology, 2 Cancer Molecular Diagnostic Core Laboratory, 3 Biotherapy Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Immunology and Biotherapy, Tianjin 300060, China.
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Cheng
authors.affiliation: 1 Department of Immunology, 2 Cancer Molecular Diagnostic Core Laboratory, 3 Biotherapy Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Immunology and Biotherapy, Tianjin 300060, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.affiliation: 1 Department of Immunology, 2 Cancer Molecular Diagnostic Core Laboratory, 3 Biotherapy Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Immunology and Biotherapy, Tianjin 300060, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wei
authors.affiliation: 1 Department of Immunology, 2 Cancer Molecular Diagnostic Core Laboratory, 3 Biotherapy Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Immunology and Biotherapy, Tianjin 300060, China.
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Yu
authors.affiliation: 1 Department of Immunology, 2 Cancer Molecular Diagnostic Core Laboratory, 3 Biotherapy Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Immunology and Biotherapy, Tianjin 300060, China.
authors.forename: Xin-Wei
authors.initials: XW
authors.lastname: Zhang
authors.affiliation: 1 Department of Immunology, 2 Cancer Molecular Diagnostic Core Laboratory, 3 Biotherapy Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Immunology and Biotherapy, Tianjin 300060, China.
authors.forename: Shui
authors.initials: S
authors.lastname: Cao
authors.affiliation: 1 Department of Immunology, 2 Cancer Molecular Diagnostic Core Laboratory, 3 Biotherapy Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Immunology and Biotherapy, Tianjin 300060, China.
authors.forename: Jin-Pu
authors.initials: JP
authors.lastname: Yu
keywords: K-ras; Non-small cell lung cancer (NSCLC); PIK3CA; meta-analysis; targeted therapy; tyrosine kinase inhibitor (TKI)