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

• Published in: PloS one 2015-05, Vol.10 (5), p.e0125791-e0125791
• Main Authors: Herman, Ana, Gruden, Kristina, Blejec, Andrej, Podpečan, Vid, Motaln, Helena, Rožman, Primož, Hren, Matjaž, Zupančič, Klemen, Veber, Matija, Verbovšek, Urška, Lah Turnšek, Tamara, Porčnik, Andrej, Koršič, Marjan, Knežević, Miomir, Jeras, Matjaž
• Format: Article
• Language: English
• Subjects: Analysis; Apoptosis; Biology; Biomarkers; Blood; Blood plasma; Blood transfusions; Brain cancer; Brain Neoplasms - blood; Brain Neoplasms - genetics; Brain Neoplasms - pathology; Brain Neoplasms - virology; Case-Control Studies; Cell cycle; Colorectal cancer; Cytomegalovirus; Diagnostic systems; Genetic aspects; Glioblastoma; Glioblastoma - blood; Glioblastoma - genetics; Glioblastoma - pathology; Glioblastoma - virology; Glioblastoma multiforme; Glioblastomas; Health aspects; Humans; Identification and classification; Immune response; Immune system; Medical diagnosis; MicroRNA; MicroRNAs; MicroRNAs - blood; MicroRNAs - genetics; miRNA; Neurosurgery; Pathogenesis; Patients; Plasma; Plasma levels; Prognosis; Proteins; Ribonucleic acid; RNA; Signaling; Studies; Survival; Survival Analysis; Testing; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0125791

Glioblastoma 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. MicroRNA 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. We 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. The 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.