Platelet transcriptomic signatures in pediatric brain tumors distinguish cancer from cancer-free control.
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Malignant pediatric brain tumors remain the leading cause of cancer-related mortality in children. Current diagnostics and monitoring rely on imaging and invasive biopsy, which may not capture tumor heterogeneity. Liquid biopsy-based biomarkers offer a novel, minimally invasive option. Among these, tumor-educated platelets have shown diagnostic value in adult cancers, but their utility in pediatric brain tumors has not been investigated. We analyzed platelet transcriptomes of 73 blood samples from 23 pediatric brain tumor patients, classified as high-grade or low-grade tumor patients, and 25 cancer-free controls. Platelets were isolated, CD45+ depleted, and subjected to 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 versus controls. Platelets from brain tumor patients showed transcriptional remodeling compared to controls, especially pronounced in high-grade tumor patients. We identified 315 and 338 differentially expressed genes in the brain tumor group versus controls and high-grade tumor patients versus control comparisons, respectively, and 9 genes in high-grade tumor patients versus low-grade tumor patients. In low-grade tumor patients versus controls, 30 genes met the significance threshold. Platelet gene expression of high-grade tumor patients showed consistent dysregulation of cancer-associated genes. Gene enrichment analyses highlighted pathways related to cytoskeleton dynamics, angiogenesis, and extracellular matrix organization. Multiple genes demonstrated encouraging classification performance, and logistic regression classifier based on selected transcripts achieved an area under the curve of 0.91, sensitivity of 85%, and a specificity of 92% in identifying high-grade tumor patients. This study provides the first evidence that platelets exhibit distinct transcriptomic signatures in pediatric brain tumor patients. Platelet RNA profiles separated high-grade tumor patients from controls, possibly reflecting tumor presence. These findings suggest that platelet transcriptomic profiling may warrant further investigation as a potential minimally invasive biomarker for pediatric brain tumors. The observed transcriptomic alterations and enriched pathways also raise the possibility that platelets participate in tumor-associated biological processes. Larger multicenter studies are needed to validate clinical applicability.