Abstract 3619: The role of CXCR4 in progression of malignant glioma

Abstract

Abstract High grade malignant gliomas are devastating, uniformly fatal cancers for which no effective therapies exist. Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. Recent studies have shown that cytokines/chemokines can regulate many malignant features of tumor cells. CXCL12/CXCR4 axis activates various signaling pathways that promote chemotaxis, adhesion and migration, cell proliferation and survival. PI3 kinase, Ras, stress-activated protein kinase (SAPK)/c-Jun Nterminal kinase (JNK), phospholipase C (PLC)/mitogen-activated protein kinase (MAPK), p38 MAPK and AKT are all downstream effectors of CXCL12/CXCR4 axis, through which tumor cell growth, dissemination and migration are facilitated. To enhance our understanding of the development and progression of glioma which may lead to novel and useful biomarkers and/or therapeutic targets in the context of GBM, we analyzed the role of CXCR4 in glioma using the published data and literature. (1).To determine the prognostic role of CXCR4 in malignant glioma, we analyzed the microarray data from Rembrandt Databases by Affymetrix HG U133 v2.0 Plus on 523 glioma patients. Kaplan-Meier analysis of overall survival showed that glioma patients with high CXCR4 expression (n=329) have short overall survival compared to those with low CXCR4 expression (n=54), logrank test: P=2.2e-8 9. Among GBM, high CXCR4 expression (n=178) have short overall survival compared to those with low CXCR4 expression (n=9), logrank test: P=0.044. Among Astrocytoma, high CXCR4 expression (n=102) have short overall survival compared to those with low CXCR4 expression (n=33), logrank test: P=0.0247 (http://www.betastasis.com/glioma/rembrandt/kaplan-meier_survival_curve/). (2).To determine the relationship between glioma progression and chemokine receptor CXCR4, we made a meta-analysis based on 14 published articles. All 14 eligible studies having 805 patients from China and USA were included. These studies showed that CXCR4 expression in glioma was correlated to high WHO grade glioma (OR=8.26, 95% CI=3.42-19.93, P<0.00001). Our results indicate that CXCR4 is a predictive marker for malignant glioma progression and survival. Suppression of CXCR4 inhibited proliferation, migration, and invasion of malignant human gliomas indicating that CXCR4 may represent a novel and promising target for therapeutic intervention of malignant glioma. Citation Format: Mingli Liu. The role of CXCR4 in progression of malignant glioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3619.