title: Ki-67 as a prognostic marker in early-stage non-small cell lung cancer in Asian patients: a meta-analysis of published studies involving 32 studies.
abstract: BACKGROUND
  Despite the large number of published papers analyzing the prognostic role of Ki-67 in NSCLC, it is still not considered an established factor for routine use in clinical practice. The present meta-analysis summarizes and analyses the associations between Ki-67 expression and clinical outcome in NSCLC patients.
  
  
  METHODS
  PubMed, Cochrane, and Embase databases were searched systematically using identical search strategies. The impacts of Ki-67 expression on survival in patients with NSCLC and NSCLC subtypes were evaluated. Furthermore, the association between Ki-67 expression and the clinicopathological features of NSCLC were evaluated.
  
  
  RESULTS
  In total, 32 studies from 30 articles met the inclusion criteria, involving 5600 patients. Meta-analysis results suggested that high Ki-67 expression was negatively associated with overall survival (OS; HR = 1.59, 95 % CI 1.35-1.88, P < 0.001) and disease-free survival (DFS; HR = 2.21, 95 % CI 1.43-3.42, P < 0.001) in NSCLC patients. Analysis of the different subgroups of NSCLC suggested that the negative association between high Ki-67 expression and OS and DFS in Asian NSCLC patients was stronger than that in non-Asian NSCLC patients, particularly in early-stage (Stage I-II) adenocarcinoma (ADC) patients. Additionally, while high expression was more common in males, smokers, and those with poorer differentiation, there was no correlation between high Ki-67 expression and age or lymph node status. Importantly, significant correlations between high Ki-67 expression and clinicopathological features (males, higher tumor stage, poor differentiation) were seen only in Asian NSCLC patients.
  
  
  CONCLUSIONS
  The present meta-analysis indicated that elevated Ki-67 expression was associated with a poorer outcome in NSCLC patients, particularly in early-stage Asian ADC patients. Studies with larger numbers of patients are needed to validate our findings.
authors.affiliation: Department of Interventional Radiology, Zhejiang tumor hospital, Hangzhou, 310022, China. songwen81@163.com.|Interventional Room of Oncology, Second Affiliated Hospital, Nanchang University, Nanchang, 330006, China. songwen81@163.com.
authors.forename: Song
authors.initials: S
authors.lastname: Wen
authors.affiliation: Department of Vascular Surgery, Second Affiliated Hospital, Nanchang University, Nanchang, 330006, China. zhouw11a@sina.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Dermatology, Second Affiliated Hospital, Nanchang University, Nanchang, 330006, China. 422784401@qq.com.
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Li
authors.affiliation: Department of Medical, Second Affiliated Hospital, Nanchang University, Nanchang, 330006, China. 283205287@qq.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Hu
authors.affiliation: Interventional Room of Oncology, Second Affiliated Hospital, Nanchang University, Nanchang, 330006, China. xiaominghuefy@163.com.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Hu
authors.affiliation: Interventional Room of Oncology, Second Affiliated Hospital, Nanchang University, Nanchang, 330006, China. wenscp2014@126.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Interventional Radiology, Zhejiang tumor hospital, Hangzhou, 310022, China. shaoguoliang666@hotmail.com.
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Shao
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital, Nanchang University, Nanchang, 330006, China. guowuhuadoctor@126.com.
authors.forename: Wu-Hua
authors.initials: WH
authors.lastname: Guo
mesh_terms: D044466:Asian People; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D017594:Publication Bias
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen