Abstract
BackgroundCD133 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.MethodsWe 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).ResultsA 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.ConclusionHigh 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.
Highlights
Glioma is the most common primary brain tumor with the most grade malignancy, in recent years the diagnosis and treatment of gliomas have made great progress, the prognosis of patients with glioma remains poor [1]
A number of studies analyze the relationship between the markers of tumor stem cells CD133, Nestin and prognosis of patients with glioma, but due to differences in research method, sample size and the study population, the findings of a single sample are difficult to extend to the entire population and the obtained conclusions are inconsistent
Studies that met all the following inclusion criteria were included in the review: (i) The diagnosis of glioma was made based on pathological examination; (ii) The association of the expression CD133 or Nestin with overall survival (OS) or progression-free survival (PFS) about gliomas was reported; (iii) The study provided the direct estimation of hazard ratios (HRs) and there was 95 % confidence intervals (CIs), or the date could be calculated by p values and other data reported. (iv) We included the studies with the largest sample size if the same glioma patient population were found to overlap among publications
Summary
Glioma is the most common primary brain tumor with the most grade malignancy, in recent years the diagnosis and treatment of gliomas have made great progress, the prognosis of patients with glioma remains poor [1]. Cancer stem cell theory considers that the occurrence of tumors derives from some special cells, these cells are called cancer stem cells with the similar characteristics to embryonic stem cells, such as selfrenewing and unlimited proliferation, multi-directional differentiation and anti-chemoradiotherapy and so on [3, 4] Due to these characteristics of cancer stem cells, the traditional treatments, such as radiation and chemotherapy, can not effectively remove the cancer stem cells, the remaining tumor stem cells continue proliferation and differentiation, leading to tumor recurrence [4, 5]. This study used Meta-analysis method to systematically evaluate the literatures on the relationship between the expression of Nestin, CD133 that were multiple markers involving glioma stem cells and the prognosis of patients with glioma. 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
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