title: Expression of CXCR4 and non-small cell lung cancer prognosis: a meta-analysis.
abstract: OBJECTIVE
  The prognostic value of aberrant C-X-C chemokine receptor type 4 (CXCR4) levels in NSCLC has been described in empirical studies. This meta-analysis evaluates the value of CXCR4 as a prognostic marker for NSCLC and determines the relationship between CXCR4 and clinicopathological features of NSCLC.
  
  
  METHODS
  A comprehensive search of the English-language literature in PubMed, Embase, Google Scholar and Web of Science was performed. Articles containing sufficient published data to determine an estimate of the hazard ratio (HR) and a 95% confidence interval (95% CI) for over survival (OS) or disease-free survival (DFS) were selected. Of 417 potentially relevant studies, 10 eligible studies (1,334 NSCLC patients) met the inclusion criteria.
  
  
  RESULTS
  Overall, high CXCR4 expression was significantly associated with a poor OS rate (HR=1.59, 95% CI=1.36-1.87, P<0.001) while the association with DFS was not statistically significant (HR=1.00, 95% CI=0.37-2.69, P=0.993). Stratified analysis by subcellular localization found that CXCR4 overexpression in the non-nucleus predicts poor OS (HR=1.65, 95% CI=1.40-1.95, P<0.001) and DFS (HR=3.06, 95% CI=2.15-4.37, P<0.001), but elevated CXCR4 expression in the nucleus was positively associated with DFS (HR=0.44, 95% CI=0.26-0.75, P=0.002). NSCLC patients with CXCR4 expression were more likely to be diagnosed with adenocarcinoma cancer (OR=1.45, 95% CI=1.07-1.95, P=0.016), lymph node involvement (OR=0.69, 95% CI=0.50-0.96, P=0.027), and distant metastasis (OR=0.36, 95% CI=0.14-0.93, P=0.035).
  
  
  CONCLUSIONS
  Aberrant overexpression of CXCR4 is associated with worse overall survival, adenocarcinoma histology, distant metastasis, lymph node involvement in NSCLC.
authors.affiliation: Center for Health Management and Policy, Key Lab of Health Economics and Policy, Ministry of Health, Shandong University 44 Wenhua Road West, Jinan 250012, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Qilu Hospital of Shandong University 107 Wenhua Road West, Jinan 250012, China.
authors.forename: Cihang
authors.initials: C
authors.lastname: Bao
authors.affiliation: Department of Healthcare Policy and Research, School of Medicine, Virginia Commonwealth University, Cancer Prevention and Control Fellow, Massey Cancer Center Richmond 980430, VA 23298-0430, US.
authors.forename: Nengliang
authors.initials: N
authors.lastname: Yao
authors.affiliation: Department of Management, School of Business, Virginia Commonwealth University 301 West Main Street, Richmond 844000, VA 23284-4000, US.
authors.forename: Chao
authors.initials: C
authors.lastname: Miao
authors.affiliation: Department of Radiation Oncology, University of Massachusetts Medical Center 434 Old Lancaster Road Sudbury, MA 01776, US.
authors.forename: John
authors.initials: J
authors.lastname: Varlotto
authors.affiliation: Center for Health Management and Policy, Key Lab of Health Economics and Policy, Ministry of Health, Shandong University 44 Wenhua Road West, Jinan 250012, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Center for Health Management and Policy, Key Lab of Health Economics and Policy, Ministry of Health, Shandong University 44 Wenhua Road West, Jinan 250012, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Sun
keywords: CXCR4; NSCLC; clinicopathological features; meta-analysis; prognosis