Analysis of Glioblastoma Patients' Plasma Revealed the Presence of MicroRNAs with a Prognostic Impact on Survival and Those of Viral Origin

Abstract

BackgroundGlioblastoma multiforme (GBM) is among the most aggressive cancers with a poor prognosis in spite of a plethora of established diagnostic and prognostic biomarkers and treatment modalities. Therefore, the current goal is the detection of novel biomarkers, possibly detectable in the blood of GBM patients that may enable an early diagnosis and are potential therapeutic targets, leading to more efficient interventions.Experimental ProceduresMicroRNA profiling of 734 human and human-associated viral miRNAs was performed on blood plasma samples from 16 healthy individuals and 16 patients with GBM, using the nCounter miRNA Expression Assay Kits.ResultsWe identified 19 miRNAs with significantly different plasma levels in GBM patients, compared to the healthy individuals group with the difference limited by a factor of 2. Additionally, 11 viral miRNAs were found differentially expressed in plasma of GBM patients and 24 miRNA levels significantly correlated with the patients’ survival. Moreover, the overlap between the group of candidate miRNAs for diagnostic biomarkers and the group of miRNAs associated with survival, consisted of ten miRNAs, showing both diagnostic and prognostic potential. Among them, hsa miR 592 and hsa miR 514a 3p have not been previously described in GBM and represent novel candidates for selective biomarkers. The possible signalling, induced by the revealed miRNAs is discussed, including those of viral origin, and in particular those related to the impaired immune response in the progression of GBM.ConclusionThe GBM burden is reflected in the alteration of the plasma miRNAs pattern, including viral miRNAs, representing the potential for future clinical application. Therefore proposed biomarker candidate miRNAs should be validated in a larger study of an independent cohort of patients.

Prevalence of Neurotropic Viruses in Malignant Glioma and Their Onco-Modulatory Potential

“…Similarly, in the present study, we found EBV DNA in three out of 45 tissues, but not in the corresponding sera, possibly due to the very low amounts of EBV. In general, low levels of viral RNA in serum would indicate chronic infection, and in line with this, we found numerous viral miRNAs in the sera of 16 patients with GBM (39). Presumably in tissues, miRNAs allow for viral persistence and appear to inhibit cellmediated immunity, apoptosis, and the cell cycle, favouring the latency of infection.…”

“…Viruses can also change the host miRNA expression patterns, and make the infected cells more prone to oncogenic transformation. Previously, we identified 11 viral miRNAs that were differentially expressed in the plasma of patients with GBM, compared to those of healthy volunteers (39). These viral miRNAs induced signalling were mostly related to impaired immune responses in the progression of GBM.…”

MicroRNA-mRNA Interactions at Low Levels of Compressive Solid Stress Implicate mir-548 in Increased Glioblastoma Cell Motility

“…5F). Downregulation of the miR181 family is associated with glioma progression 31 , whereas the miR548 family is associated with prognosis and survival 32,33 . These results suggest that both families are potential therapeutic targets.…”

A comprehensive proteomic SWATH-MS workflow for profiling blood extracellular vesicles: a new avenue for glioma tumour surveillance

“…PPIA, also known as cyclophilin A, has roles across a range of biological processes, with essential functions in protein folding and chaperone activity [73]. PPIA overexpression is reported in various cancer types, its expression is influenced by chemotherapy [74,75] and PPIA has been reported to be a target gene of dysregulated miRNA species that are present in the plasma of GBM patients [76]. C3 is a member of the human complement system with key functions in innate immunity.…”