Nestin Expression Is Associated With Poor Prognosis And WHO Grade In Glioma Patients: A Meta-analysis

Introduction:Glioma is the most prevalent type of primary central nervous system tumor in adults. Despite intense efforts to optimize the treatment of gliomas, the relapse rate is still very high because of its biological characteristics, so the prognosis of glioblastoma patients still remains frustrating. Thus, it is imperative to find a biomarker to assess the prognosis of glioma patients. Recent reports indicate that there are a population of tumor cell with stem cell properties, referred to as cancer stem cells(CSCs), which play an important role in the tumorigenesis, multiplication, recurrence and resistance to chemotherapy and radiotherapy. Nestin is classified as a class VI IF protein, whose expression is shown mainly in neural and muscular stem ? progenitor cells, with the expression decreasing as the cells differentiate. It is one of the most commonly studied stem cell biomarkers. So far, there are numerous independent studies trying to evaluate the prognostic value of nestin for glioma. However, because of methodological difference various sample size and demographic differences of their research objects, the prognostic value of nestin for glioma remains controversial.Objective:To objectively and systematically evaluate the prognostic significance of nestin in glioma patients and its association with WHO grade of glioma by conducting a Meta-analysis.Methods:A systematic literature search of Pub Med/Medline, Web of Science, Cochrane Library and Google scholar was performed to recruit studies between January 1990 and December 2015 that evaluated the correlation of nestin with overall survival(OS) and progression-free survival(PFS) and its association with WHO grade in glioma patients. A Meta-analysis(R-3.1.3) was conducted to analyze the prognostic significance of nestin in glioma patients.Results:A total of 12 studies with the total number of 1735 patients met inclusion criteria. The analysis demonstrated negative associations between nestin high expression and both poor OS(hazard ratio [HR]=1.64, 95% confidence interval [CI] =1.27-2.12, P=0.0001) and PFS(HR=1.54, 95%CI=1.04-2.28, P=0.0301). WHO grading was the main source of heterogeneity of OS data(P=0.0015), and the lower the WHO grade, the more significant the influence in OS. The sample capacity was the main source of heterogeneity of PSF data(P=0.008), and the larger the sample capacity, the more significant the influence in PFS. Compared with low grade glioma, there is a higher expression of nestin in the samples of high grade glioma(OR=3.07,CI= 2.21~4.26,P=0.0001).Conclusion:Nestin expression can be used for accurately assessing the survival of glioma patients, thus, nestin could be recommended as a useful survival biomarker in clinical practice. The results of subgroup analyses show that WHO grade and sample size were potential causes of heterogeneity. Nestin expression is also associated with WHO grade of glioma.