CBM-16TUMOR-EDUCATED PLATELET-BASED LIQUID BIOPSIES IN GLIOBLASTOMA PATIENTS

INTRODUCTION: Blood-based liquid biopsies are a potential approach for leveraging clinical cancer diagnostics and patients' treatment. However, so far, diagnostic, prognostic, predictive, and monitoring biomarkers for patients with diffuse glioma are only limitedly available, and require further validation. Tumor-educated blood platelets (TEPs) sequester several biomolecules, including EGFRvIII mRNA, during tumor growth, thereby altering their RNA profile. Therefore, we reasoned that TEPs may serve as an potential biosource for blood-based biomarkers. METHODS: Blood platelets of patients with glioblastoma and healthy individuals were isolated and subjected to total RNA isolation. Platelet mRNA was amplified using full-length SMARTer mRNA amplification, and processed for sequencing on the Illumina platform. Raw sequencing data was aligned and summarized to the human reference genome using STAR and HTseq, and subjected to differential expression analyses, hierarchical clustering and support vector machine (SVM) classification. RESULTS: We characterized the platelet RNA of 39 glioblastoma patients, and 52 healthy individuals by high-throughput RNA-sequencing. Glioblastoma patient-derived TEPs contained 457 RNAs (FDR < 0.001) that were differentially expressed as compared to healthy individuals. Gene ontology showed that these RNAs are implicated in several biological processes such as RNA translation, immune response, and DNA repair. Using SVM classification we readily separated both groups from each other (accuracy: 94%, AUC: 0.982). CONCLUSIONS AND FUTURE EXPERIMENTS: Our results suggest that TEPs harbour potential as a diagnostic biosource. To further evaluate the biomarker potential, follow-up studies using additional samples, including samples of lower grade glioma and brain metastases patients are under way. Furthermore, we have initiated the collection of clinical follow-up platelet samples to identify the potential of TEPs as disease monitoring biomarkers in glioma patients. Eventually, we believe TEPs have the potential to guide clinical decision making in every day practice.