title: Do relevant markers of cancer stem cells CD133 and Nestin indicate a poor prognosis in glioma patients? A systematic review and meta-analysis.
abstract: BACKGROUND
  CD133 and Nestin, as the markers of cancer stem cells, have recently been reported frequently in the pathogenesis and development of human gliomas. However, the prognostic role of CD133 and Nestin in gliomas still remains controversial. In this study, we aimed to evaluate the association between the expression of CD133 and Nestin and the outcome of glioma patients by conducting a systematic review and meta-analysis.
  
  
  METHODS
  We performed systematically electronic and manual searches through the database of Pubmed and embase (until to December 25, 2014) for titles and abstracts which investigated the relationships between CD133 and Nestin expression and outcome of glioma patients. A systematic review and meta-analysis was executed to generate Pooled hazard ratios (HRs) with 95 % confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS).
  
  
  RESULTS
  A total of 1,490 patients from 32 studies (13 articles) were included in the analysis. 19 studies and 13 studies investigated correlation between CD133 expression or Nestin and survival in gliomas, respectively. Our results showed that high CD133 expression in patients with glioma was associated with poor prognosis in terms of OS (HR 1.69; 95 % CI, 1.16-2.47; P =0.0060) and PFS (HR, 1.64; 95 % CI, 1.12-2.39; P = 0.010). In addition, high Nestin expression were associated with worse OS (HR 1.751; 95 % CI, 1.19-2.58, p = 0.004) but has no significant association with PFS (HR 1.55; 95 % CI, 0.96-2.51, p = 0.074). Even more important, the results of the subgroup meta-analyses show that that high CD133 expression was associated with worse prognosis in terms of OS and PFS in patients with WHO IV glioma but not WHO II-III. On the other hand, Nestin high expression was associated with worse prognosis in terms of OS and PFS in patients with WHO II-III glioma but not WHO IV.
  
  
  CONCLUSIONS
  High level of CD133 expression trends to correlate with a worse OS and PFS in glioma patients, especially WHO IV gliomas and Nestin high expression trends to correlate with a worse OS in glioma patients especially WHO II-III, revealing both the markers of cancer stem cells may as the potential pathological prognostic markers for glioma patients.
authors.affiliation: Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, Zhejiang Province, 310022, China. Wubintop@sina.cn.
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.affiliation: Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, Zhejiang Province, 310022, China. 2226124552@qq.com.
authors.forename: Caixing
authors.initials: C
authors.lastname: Sun
authors.affiliation: Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, Zhejiang Province, 310022, China. 408318197@qq.com.
authors.forename: Fang
authors.initials: F
authors.lastname: Feng
authors.affiliation: Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, Zhejiang Province, 310022, China. f38865319@dlmu.edu.cn.
authors.forename: Minghua
authors.initials: M
authors.lastname: Ge
authors.affiliation: Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, Zhejiang Province, 310022, China. xialiang@zjcc.org.cn.
authors.forename: Liang
authors.initials: L
authors.lastname: Xia
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor; D005260:Female; D015870:Gene Expression; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D064231:Nestin / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D017594:Publication Bias; D016019:Survival Analysis
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; D064231:Nestin; C000606023:PROM1 protein, human; D010455:Peptides