Platelet transcriptomic signatures in pediatric brain tumors distinguish cancer from cancer-free control

Background Malignant pediatric brain tumors remain the leading cause of cancer-related mortality in children. Current diagnostics rely on imaging and invasive biopsy, which may not capture tumor heterogeneity. Liquid biopsy-based biomarkers such as tumor-educated platelets have shown diagnostic value in adult cancers, but their utility in pediatric brain tumors has not been investigated. Methods We analyzed platelet transcriptomes of 73 blood samples from 23 pediatric brain tumor patients, classified as high-grade tumor patients or low-grade tumor patients, and 25 cancer-free controls. Platelets were isolated, CD45⁺ depleted, and RNA was extracted for RNA sequencing. CD45⁺ depletion efficiency was assessed using xCell-based leukocyte enrichment scores. Differential gene expression was assessed with DESeq2 and Gene Ontology over-representation analysis. Gene-level discrimination between groups was evaluated by receiver operating characteristic analysis, and a logistic regression model with patient-grouped 5-fold cross-validation was trained to classify high-grade tumor patients vs. controls. Results Platelets from brain tumor patients showed transcriptional remodeling compared to controls, especially pronounced in high-grade tumor patients. We identified 398 and 649 differentially expressed genes in the brain tumor group vs. controls and high-grade tumor patients vs. control comparisons, respectively, and 85 genes in high-grade tumor patients vs. low-grade tumor patients. No genes met significance in low-grade tumor patients vs. controls. High-grade tumor patients showed consistent upregulation of cancer-associated mitochondrial genes. Similarly, gene enrichment analyses highlighted pathways related to mitotic regulation, chromosome segregation, and mitochondrial metabolism. Multiple genes demonstrated strong diagnostic performance, and logistic regression classifier based on selected platelet transcripts achieved an area under the curve of 0.89, sensitivity of 79%, and a specificity of 80% in identifying high-grade tumor patients. Conclusions This study provides the first evidence that platelets exhibit distinct transcriptomic signatures in pediatric brain tumor patients. Platelet RNA profiles robustly differentiate high-grade tumor patients from low-grade tumor patients and cancer-free controls, reflecting tumor presence and biological aggressiveness. These findings support the feasibility of tumor-educated platelets as a minimally invasive biomarker for pediatric malignant brain tumor detection, and longitudinal monitoring. Larger multicenter studies are warranted to validate applicability.