CXCL12 and CXCR4 as predictive biomarkers of glioma recurrence pattern after total resection

Pathol Biol (Paris). 2015 Sep;63(4-5):190-8. doi: 10.1016/j.patbio.2015.07.002. Epub 2015 Aug 14.

Abstract

Purpose of the study: 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.

Patients and 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.

Conclusion: 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.

Keywords: CXCL12; CXCR4; CXXR4; Gliomas; Gliome; Recurrence pattern; Récidive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Antineoplastic Agents / therapeutic use
  • Brain Neoplasms / chemistry*
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy
  • Chemokine CXCL12 / analysis*
  • Chemokine CXCL12 / genetics
  • Chemoradiotherapy
  • Cranial Irradiation
  • Craniotomy
  • Disease-Free Survival
  • Endothelial Cells / chemistry
  • Glioma / chemistry*
  • Glioma / diagnostic imaging
  • Glioma / genetics
  • Glioma / pathology
  • Glioma / therapy
  • Humans
  • Kaplan-Meier Estimate
  • Magnetic Resonance Imaging
  • Multimodal Imaging
  • Neoplasm Invasiveness
  • Neoplasm Proteins / analysis*
  • Neoplasm Proteins / genetics
  • Neoplasm Recurrence, Local / chemistry*
  • Neoplasm Recurrence, Local / diagnostic imaging
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / therapy
  • Neuroimaging
  • Prognosis
  • Proportional Hazards Models
  • Receptors, CXCR4 / analysis*
  • Receptors, CXCR4 / genetics
  • Tomography, X-Ray Computed
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • CXCL12 protein, human
  • CXCR4 protein, human
  • Chemokine CXCL12
  • Neoplasm Proteins
  • Receptors, CXCR4