Relationship between chemokine/chemokine receptor and glioma prognosis and outcomes: Systematic review and meta-analysis

Glioma is a primary tumor originating from the central nervous system, and despite ongoing efforts to improve treatment, its overall survival rate remains low. There are a limited number of reports regarding the clinical grading, prognostic impact, and utility of chemokines. Therefore, conducting a meta-analysis is necessary to obtain convincing and conclusive results. A comprehensive literature search was conducted using various databases, including PubMed, Web of Science, The Cochrane Library, Embase, Ovid Medline, CNKI, Wanfang Database, VIP, and CBM. The search encompassed articles published from the inception of the databases until March 2024. The estimated odds ratio (ORs), standard mean difference (SMDs), and hazard ratio (HR) with their corresponding 95% confidence intervals (95% CI) were calculated to assess the predictive value of chemokine and receptor levels in glioma risk. Additionally, heterogeneity tests and bias tests were performed to evaluate the reliability of the findings. This meta-analysis included a total of 36 studies, involving 2,480 patients diagnosed with glioma. The results revealed a significant association between the expression levels of CXCR4 (n = 8; OR = 22.28; 95 % CI = 11.47–43.30; p = 0.000), CXCL12 (n = 4; OR = 10.69; 95 % CI = 7.03–16.24; p = 0.000), CCL2 (n = 6; SMD = -0.83; 95 % CI = -0.98‐-0.67; p = 0.000), CXCL8 (n = 3; SMD = 0.75; 95 % CI = 0.47–1.04; p = 0.000), CXCR7 (n = 3; OR = 20.66; 95 % CI = 10.20–41.82; p = 0.000), CXCL10 (n = 2; SMD = 3.27; 95 % CI = 2.91–3.62; p = 0.000) and the risk of glioma. Additionally, a significant correlation was observed between CXCR4 (n = 8; OR = 4.39; 95 % CI = 3.04–6.32; p = 0.000), (n = 6; SMD = 1.37; 95 % CI = 1.09–1.65; p = 0.000), CXCL12 (n = 6; OR = 6.30; 95 % CI = 3.87–10.25; p = 0.000), (n = 5; ES = 2.25; 95 % CI = 1.15–3.34; p = 0.041), CCL2 (n = 3; OR = 9.65; 95 % CI = 4.55–20.45; p = 0.000), (n = 4; SMD = -1.47; 95 % CI = -1.68--1.26; p = 0.000), and CCL18 (n = 3; SMD = 1.62; 95 % CI = 1.30–1.93; p = 0.000) expression levels and high-grade glioma (grades 3-4). Furthermore, CXCR4 (HR = 2.38, 95 % CI = 1.66–3.40; p = 0.000) exhibited a strong correlation with poor overall survival (OS) rates in glioma patients. The findings of this study showed a robust association between elevated levels of CXCR4, CXCL12, CCL2, CXCL8, CXCL10 and CXCR7 with a higher risk of glioma. Furthermore, the WHO grading system was validated by the strong correlation shown between higher expression of CXCR4, CXCL12, CCL2, and CCL18 and WHO high-grade gliomas (grades 3-4). Furthermore, the results of the meta-analysis suggested that CXCR4 might be a helpful biomarker for predicting the worse prognosis of glioma patients.