Urine and cerebrospinal fluid biomarkers for early glioma detection: a systematic review

Background Liquid biopsies offer a minimally invasive approach for early glioma detection. However, potential non-blood biomarkers in urine and CSF are under-researched. While urine is easier to sample and has fewer proteins/cells, CSF may yield higher detection rates due to its proximity to the glioma. This systematic review evaluates non-blood liquid biopsy biomarkers (proteins, metabolites, cell-free DNA, and miRNA) in urine and CSF for early glioma detection. Methods Three electronic databases (MEDLINE, Embase, and BIOSIS) were searched from inception to September 2024. Studies which assessed urine- or CSF-derived biomarkers as a means of identifying glioma patients were included. The primary outcomes of interest were measures of diagnostic test accuracy (specificity, sensitivity, positive predictive value, negative predictive value and area under the ROC curve). QUADAS-2 was used to assess risk of bias in included studies. Results We extracted data from 20 studies (669 glioma patients and 597 controls) which met the inclusion criteria. Five of the included studies investigated urine-derived biomarkers, and 15 investigated CSF-derived biomarkers. Meta-analysis was not possible due to the heterogeneous nature of biomarkers collected, analysis methods, and differences in patient demographics. Conclusions Conclusions are limited by the paucity of studies and small sample sizes. These limitations highlight the need for well-designed, adequately powered studies to evaluate the diagnostic utility of urine and CSF for glioma liquid biopsies.