Peripheral Blood Leukocyte Ratios as Novel Biomarkers in Brain Glioma: A Comprehensive Systematic Review and Meta‐Analysis

Inflammatory biomarkers, such as leukocyte ratios, have emerged as promising tools for diagnosing and prognosticating brain gliomas. This study systematically reviewed and analysed the diagnostic and prognostic relevance of peripheral blood leukocyte ratios in glioma. Following the PRISMA guidelines, we conducted a systematic review and meta-analysis by searching PubMed, Web of Science, and Scopus for studies published in English. Eligible studies evaluated the sensitivity, specificity, and area under the curve (AUC) of inflammatory ratios, as well as their associations with survival outcomes. Quality was assessed using the Newcastle-Ottawa Scale. A total of 29 assessments with 13,189 observations compared the neutrophil-to-lymphocyte ratio (NLR) between glioma patients and non-glioma groups, yielding a pooled standardised mean difference (SMD) of 0.445 (95% CI: 0.280-0.609, p < 0.0001; I² = 85.1%). When compared to healthy individuals (10 assessments, 4444 observations), glioma patients exhibited a significantly elevated NLR (SMD: 0.797, 95% CI: 0.576-1.019, p < 0.0001; I² = 87.5%). Compared to meningioma (5 assessments, 3227 observations), glioma patients had a significantly higher NLR (SMD: 0.352, 95% CI: 0.280-0.424, p < 0.0001; I² = 24.7%). In comparisons with brain metastasis (4 assessments, 428 observations), the difference was not significant (SMD: -0.112, p = 0.3315; I² = 44.6%). The platelet-to-lymphocyte ratio (PLR) (25 assessments, 12,085 observations) showed no significant difference between glioma and non-glioma groups (SMD: 0.1291, p = 0.0836; I² = 81.4%). Similarly, the derived NLR (dNLR) was significantly higher in glioma patients than in non-glioma groups (SMD: 0.2421, p < 0.0001; I² = 49.9%). The lymphocyte-to-monocyte ratio (LMR) was significantly lower in glioma compared to meningioma (SMD: -0.2989, p < 0.0001; I² = 0.0%). MLR analysis showed high heterogeneity (I² = 99.5%) with non-significant findings (p = 0.4476). These findings suggest NLR and dNLR as potential biomarkers for glioma diagnosis. Peripheral blood leukocyte ratios, particularly NLR, represent valuable biomarkers for glioma diagnosis and prognosis. Further research is warranted to enhance their precision and clinical utility.