Studies On The Correlation Between FBP1 And Glioma

Objective1. To investigate the expression of FBP1 in human glioma and the correlation with proliferation marker Ki-67, c-Myc and their clinicopathologic significance. Besides, discuss the effect of FBP1 in the occurrence and the development of glioma.2. To evaluate the particular effect of FBP1 during glioma cell growth.Methods1. Western blot and immunohistochemical analysis were used to detect the expression levels of FBP1, c-Myc and Ki-67 in glioma tissue. The glioma tissue included: 70 paraffin glioma cases, nine fresh human astrocytic tumors samples and three normal brain specimens were acquired from patients undergoing surgery for epilepsy. All analyses were carried out using SPSS13.0 statistical software.2. Serum starvation and release were used to analyze cell cycle. The expression and cellular localization of FBP1 and c-Myc were detected by western blot and immunofluorescence analysis. Small interfering RNA technology was used to treat U87 MG cell and U251 MG cell to silence FBP1 gene expression, the expression of FBP1 and c-Myc were investigated by western blot and immunoflurescence. CCK8 and flow cytometry analysis were used to analyze its impact on glioma cell growth.Results1. FBP1 expression directly correlated with pathologic grade of glioma(P=0.013). However, no significant difference were seen regarding patients’ age, gender, KPS score, tumor location, type of surgery, tumor diameter, vessel density, or necrosis. By Spearman analysis, we noticed that FBP1 expression is positively associated with c-Myc(γ=0.740, P=0.005) and Ki-67 expression(γ=0.830, P=0.009) in all cases of glioma analyzed. We also determined a positive correlation between c-Myc and Ki-67 expression(γ=0.732; P=0.000). Furthermore, we found that patients in the low expression FBP1(0-3) group have significantly higher overall survival than the high expression FBP1(4-7) group(P=0.004) by Kaplan–Meier analysis. The Cox’s proportional hazards model suggested that FBP1 might be a novel prognostic factor in a subset of patients with glioma(P=0.037).2. Following serum stimulation of starved glioma cells, the expression of FBP1 was upregulated, as well as c-Myc. Moreover, knockdown of FBP1 by si RNA transfection diminished the expression of c-Myc and arrested cells growth.Conclusions1. The expression of FBP1 was directly correlated with the grade of glioma. FBP1 expression is positively associated with c-Myc and Ki-67 expression in all cases of glioma analyzed. It suggests that disregulation of FBP1 may promote cell proliferation, thus may play key roles in the occurrence and development of glioma.2. We also found that the close correlation between FBP1 expression and patient survival, and indicated that prognostic significance of FBP1 expression in glioma.3. FBP1 may regulate glioma cell growth possibly by regulating cell cycle and the level of c-Myc. It indicates FBP1 may act as an oncogene in glioma.4. We used small interfering RNA technology to silence FBP1 gene expression and demonstrated that knock-down of FBP1 significantly decreased the cell cycle progression of glioma cells, thus inhibiting the growth of glioma. These observations indicate that the FBP1 gene represent a potential novel target for pharmaceutical treatment of human brain glioma.