Exosomes are nano-sized extracellular vesicles released by many cells that contain molecules characteristic of their cell of origin, including
microRNA. Exosomes released by
glioblastoma cross the blood-brain barrier into the peripheral circulation and carry molecular cargo distinct to that of "free-circulating"
miRNA. In this pilot study, serum exosomal
microRNAs were isolated from
glioblastoma (n = 12) patients and analyzed using unbiased deep sequencing. Results were compared to sera from age- and gender-matched healthy controls and to grade II-III (n = 10)
glioma patients. Significant differentially expressed
microRNAs were identified, and the predictive power of individual and subsets of
microRNAs were tested using univariate and multivariate analyses. Additional sera from
glioblastoma patients (n = 4) and independent sets of healthy (n = 9) and non-
glioma (n = 10) controls were used to further test the specificity and predictive power of this unique exosomal
microRNA signature. Twenty-six
microRNAs were differentially expressed in serum exosomes from
glioblastoma patients relative to healthy controls. Random forest modeling and data partitioning selected seven
miRNAs (miR-182-5p, miR-328-3p, miR-339-5p, miR-340-5p, miR-485-3p, miR-486-5p, and miR-543) as the most stable for classifying
glioblastoma. Strikingly, within this model, six iterations of these
miRNA classifiers could distinguish
glioblastoma patients from controls with perfect accuracy. The seven
miRNA panel was able to correctly classify all specimens in validation cohorts (n = 23). Also identified were 23 dysregulated
miRNAs in IDHMUT
gliomas, a partially overlapping yet distinct signature of lower-grade
glioma. Serum exosomal
miRNA signatures can accurately diagnose
glioblastoma preoperatively.
miRNA signatures identified are distinct from previously reported "free-circulating"
miRNA studies in GBM patients and appear to be superior.