C-C motif chemokine ligand 2/C-C receptor 2 is associated with glioma recurrence and poor survival

Abstract

Several studies have explored the mechanisms of C-C motif chemokine ligand (CCL)2/CC receptor (R)2 function in tumorigenesis and inflammation. However, little is known about the role of CCL2/CCR2 in tumor recurrence, especially after radiotherapy. The present study aimed to determine the association between CCL2/CCR2 and glioma relapse. Moreover, the difference in the expression of CCL2/CCR2 between post-radiation and non-radiation recurrent glioma tissues was compared. A retrospective analysis of 80 patients with glioma who underwent tumor resection twice was performed. Primary group refers to glioma patients who received glioma resection surgery for the first time. Recurrent group refers to glioma patients who received glioma resection surgery after first relapse. In total, 10 patients with brain trauma who underwent partial resection of the normal brain as decompression treatment were used as controls. Protein expression levels of CCL2 and CCR2 were evaluated using immunohistochemistry. Prognostic analyses of patient survival using Kaplan-Meier curves and Cox regression models were performed. The expression levels of CCL2 and CCR2 were higher in recurrent glioma compared with the primary group. There was a positive correlation between tumor grade and protein expression of CCL2/CCR2. Furthermore, irradiation had a significant effect on CCR2 protein expression (P=0.014), but not on CCL2 protein expression (P=0.626). However, the expression of CCL2 and CCR2 showed no significant difference between primary and secondary glioblastoma. After adjusting for sex, radiotherapy and location of tumors in these gliomas, CCL2 was a prognostic factor for disease-free and overall survival (OS) times, as well as age and tumor grade. In the multivariate Cox modeling for glioma, CCR2 was significantly associated with OS rather than DFI. The significant correlations between CCL2/CCR2 expression and glioma tumor grade suggested that CCL2/CCR2 has a role in glioma progression. Combined with previous in vitro experiments, it was proposed that irradiation (radiotherapy)-induced expression of CCL2 is transient, while irradiation-induced expression of CCR2 is lasting. Therefore, CCL2/CCR2 is a potential therapeutic target for patients with glioma.