A Network Story: tumor educated platelets transcriptome and Glioblastoma

Motivation: Tumor-educated platelets (TEPs) are emerging as a promising liquid biopsy source for cancer detection and monitoring. However, it remains unclear whether their transcriptomic alterations reflect tumor-specific molecular mechanisms or broader systemic responses. In particular, their relationship with the molecular network underlying glioblastoma (GBM) has not been systematically investigated. Objective: The aim of this study is to assess whether transcriptomic alterations in TEPs from GBM patients are functionally and topologically associated with the GBM disease module in the human interactome. Methods: RNA-seq data from TEPs (GSE68086) were analyzed to identify differentially expressed genes (DEGs) between GBM patients and healthy controls (adjusted p-value < 0.01, |log2FC| ≥ 0.5), yielding 1401 DEGs. After gene mapping and filtering, 1298 non-overlapping DEGs were projected onto a human protein-protein interaction network from BioGRID. A curated set of 48 GBM seed genes from IntOGen defined the disease module. Network proximity was computed as the mean shortest-path and compared against 500 random gene sets. Random walk with restart (0.7) was applied to prioritize DEGs. Results: DEGs showed significant proximity to GBM genes (mean distance 1.41 vs 1.66 expected; Z = -18.69; p < 0.002). Functional enrichment highlighted telomere maintenance, DNA repair, transcriptional regulation, cell cycle, and stress response pathways. Conclusion: TEP transcriptomic alterations in GBM are non-randomly organized and closely linked to the GBM disease module.