Expression Of CXCL12/CXCR4 And Their Influence On Glioma Recurrence Pattern Or Peritumoral Brain Edema

Part 1: CXCL12 and CXCR4 as predictive biomarkers of glioma recurrence pattern after total resection Purpose: Previous studies have shown that the pattern of recurrence for glioma is related to the direction of glioma cell invasion. Recent studies demonstrated that the CXCL12-CXCR4 signaling pathway mediates cellular invasion in glioma. Therefore, in this study, we investigated the possible relationship between CXCL12/CXCR4 expression and recurrence pattern in glioma. Methods: Immunohistochemical techniques were used to assess CXCL12/CXCR4 expression in 42 glioma tissues following total resection. According to magnetic resonance imaging(MRI) of gliomas, the recurrence pattern was classified as close or distant pattern. The relationship between recurrence pattern and CXCL12/CXCR4 expression were initially examined by chi-squared analysis. The prognostic significance of CXCL12 and CXCR4 was determined by log-rank tests and COX proportional hazards model. Results: CXCL12 was expressed mainly in vascular endothelial cells and CXCR4 was expressed mainly in tumor cells. The recurrence pattern was significantly related to the expression level of CXCL12 in vascular endothelial cells(P = 0.002) and CXCR4 in tumor cells(P = 0.004). However, CXCL12 and CXCR4 were not independent prognostic factors for progression-free survival or overall survival in glioma patients. Conclusions: The glioma recurrence pattern is related to CXCL12 expression levels in vascular endothelial cells and CXCR4 expression levels in tumor cells; thus, implicating the CXCL12-CXCR4 signaling pathway as a potential target for glioma therapy.Part 2: Expression of CXCL 12 and CXCR4 in gliomas and their influence on peritumoral brain edemaObjective: To evaluate the relationship between CXC-motif-chemokine 12/C-X-C receptor 4(CXCL12/CXCR4) expression and peritumoral brain edema(PTEB) in glioma patients. Methods: Immunohistochemical techniques were used to detect the expression of CXCR4 and CXCL12 in 42 glioma tissues. MRI was used to evaluate the extent and type of brain edema in preoperative glioma patients. The relationship between edema and CXCL12/CXCR4 expression was examined by chi-squared analysis. The prognostic significance of CXCL12 or CXCR4 was determined by log-rank tests and COX proportional hazards model. Result: Expression of CXCL12 and CXCR4 was observed in vascular endothelial cells and tumor cells. The degree(P = 0.033) and morphology(P = 0.033) of PTEB were significantly associated with the level of CXCL12 expression in vascular endothelial cells. The degree(P = 0.001) and morphology(P = 0.004) of PTBE were associated with the level of CXCR4 expression in tumor cells. CXCL12-positive tumor cells(P = 0.006) and CXCR4-positive vascular endothelial cells(P = 0.030) were significantly associated only with the degree of edema. Multivariate analysis showed that CXCL12 and CXCR4 were not independent prognostic factors of progression-free survival(PFS) or overall survival(OS) in glioma patients. Conclusion: The levels of CXCL12 expression in vascular endothelial cells and CXCR4 expression in tumor cells are associated with PTEB, indicating that the CXCL12-CXCR4 signaling pathway is a potential target for glioma therapy.