Abstract
BackgroundEvidence suggests that cytoglobin (Cygb) may function as a tumor suppressor gene.MethodsWe immunohistochemically evaluated the expression of Cygb, phosphatidylinositol-3 kinase (PI-3K), phosphorylated (p)-Akt, Interleukin-6 (IL-6), tumor necrosis factor-α (TNFα) and vascular endothelial growth factor (VEGF) in 88 patients with 41 high-grade gliomas and 47 low-grade gliomas. Intratumoral microvessel density (IMD) was also determined and associated with clinicopathological factors.ResultsLow expression of Cygb was significantly associated with the higher histological grading and tumor recurrence. A significant negative correlation emerged between Cygb expression and PI3K, p-Akt, IL-6, TNFα or VEGF expression. Cygb expression was negatively correlated with IMD. There was a positive correlation between PI3K, p-Akt, IL-6, TNFα and VEGF expression with IMD.High histologic grade, tumor recurrence, decreased Cygb expression, increased PI3K expression, increased p-Akt expression and increased VEGF expression correlated with patients’ overall survival in univariate analysis. However, only histological grading and Cygb expression exhibited a relationship with survival of patients as independent prognostic factors of glioma by multivariate analysis.ConclusionsCygb loss may contribute to tumor recurrence and a worse prognosis in gliomas. Cygb may serve as an independent predictive factor for prognosis of glioma patients.
Highlights
Evidence suggests that cytoglobin (Cygb) may function as a tumor suppressor gene
Immunohistochemical assessment of Cygb, Phosphatidylinositol-3 kinase (PI3K), p-Akt, IL-6, tumor necrosis factor-α (TNFα) and vascular endothelial growth factor (VEGF) in gliomas Cytoplasmic and nucleus surface positive staining for Cygb, PI3K and p-Akt was observed in tumor cells of gliomas, no positive staining was shown in tumor cells of negative controls (Figure 1)
Immunostaining signal of IL-6, TNFα and VEGF was localized in the cytoplasm of tumor cells (Figure 2) and CD34 was localized in endothelial cells of newly formed vessels
Summary
Evidence suggests that cytoglobin (Cygb) may function as a tumor suppressor gene. Glioma is the most common brain tumor in adults. IL-6 is implicated as major regulators of glioma cell growth and invasiveness. IL-6 cytokine has been extensively studied in astroglial tumors at the mRNA [19] and protein level [20,21] and has been proposed as a determinant of brain tumor progression [22]. It has been shown in experimental models that development of glioblastoma requires the presence of IL-6 [23]. Knowing that IL-6 functions as a downstream mediator for tumor necrosis factor-α (TNF-α) [24], IL-6 is recognized as potent regulators of angiogenesis [vascular endothelial growth factor (VEGF)] [25]. The paucity of prognostic information regarding Cygb expression and the prognostic role of PI3K/Akt signaling in gliomas prompted us to undertake the present study
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