Cell-Free Plasma MicroRNAs that Identify Patients with Glioblastoma

This retrospective multicenter pilot study aims to determine potential cell-free microRNAs (cfmiRs) that identify patients with primary GBM (pGBM) tumors and to monitor Glioblastoma (GBM) recurrence. Overall design: CfmiRs were detected in pre-operative plasma samples from patients with pGBM (n=32) and recurrent GBM (rGBM, n=13) using the HTG miRNA whole transcriptome assay (WTA) assessing for 2,083 miRs. As controls plasma samples from normal healthy donors (NHD, n=73) were assessed. 265 cfmiRs were found differentially expressed (DE) in plasma samples from pGBM patients compared to NHDs (FDR <0.05). Additionally, we found 179 cfmiRs DE in rGBM, of which 68 cfmiRs were commonly DE in pGBM. Using Random Forest algorithm, specific cfmiR classifiers were found in the plasma of pGBM, rGBM, and both pGBM and rGBM combined. Two common cfmiR classifiers, miR-3180-3p and miR-5739, were found in all of the comparisons. In receiving operating characteristic (ROC) curves analysis for rGBM miR-3180-3p showed a specificity of 87.7% and a sensitivity of 100% (AUC=98.5%); while miR-5739 had a specificity of 79.5% and sensitivity of 92.3% (AUC=90.2%). This study demonstrated that pGBM and rGBM plasma have specific miR-signatures. CfmiR-3180-3p and cfmiR-5739 have potential utility in diagnosing patients with pGBM tumors and monitoring GBM recurrence using a minimally invasive blood assay.