The plasma miRnome and venous thromboembolism in high-grade glioma: miRNA sequencing of a nested case-control cohort

Background: Patients with high-grade gliomas are at high risk of venous thromboembolism (VTE). MicroRNAs (miRNAs) are small non-coding RNAs with multiple roles in tumor biology, hemostasis and platelet function. We aimed to explore the association between plasma miRNAs and risk of VTE in high-grade glioma. Results: We conducted a nested-case control study within 152 patients with WHO grade IV glioma that had been included in the Vienna Cancer and Thrombosis Study (CATS), a prospective cohort study focused on risk factors for VTE in newly diagnosed or recurrent cancer. At study inclusion a single blood draw was taken, and patients were thereafter followed for a maximum of two years. During that time, 24 patients (16%) developed VTE. Of the other 128 patients, we randomly selected 24 age- and sex-matched controls. After sample quality control, the final group size was 21 VTE-patients and 23 without VTE. Small RNA next-generation sequencing of plasma was performed. We observed that hsa-miR-451a was globally the most abundant miRNA. Notably, 51% of all miRNAs showed a correlation with platelet count. The analysis of miRNAs differentially regulated in VTE patients – with and without platelet adjustment – identified potential VTE biomarker candidates such as has-miR- 221-3p. Conclusion: We here provide one of the largest and deepest peripheral blood miRNA datasets of high-grade glioma patients so far. Further, we confirm previous observations of a considerable impact of platelet count on the blood miRNome. And, finally, we present first VTE biomarker candidates that can serve as the starting point for future confirmatory research. miRNA sequencing of a nested case-control cohort