Exosomal levels of miRNA-21 from cerebrospinal fluids associated with poor prognosis and tumor recurrence of glioma patients

Oncotarget. 2015 Sep 29;6(29):26971-81. doi: 10.18632/oncotarget.4699.

Abstract

Glioma is a most common type of primary brain tumors. Extracellular vesicles, in the form of exosomes, are known to mediate cell-cell communication by transporting cell-derived proteins and nucleic acids, including various microRNAs (miRNAs). Here we examined the cerebrospinal fluid (CSF) from patients with recurrent glioma for the levels of cancer-related miRNAs, and evaluated the values for prognosis by comparing the measures of CSF-, serum-, and exosome-contained miR-21 levels. Samples from seventy glioma patients following surgery were compared with those from brain trauma patients as a non-tumor control group. Exosomal miR-21 levels in the CSF of glioma patients were found significantly higher than in the controls; whereas no difference was detected in serum-derived exosomal miR-21 expression. The CSF-derived exosomal miR-21 levels correlated with tumor spinal/ventricle metastasis and the recurrence with anatomical site preference. From additional 198 glioma tissue samples, we verified that miR-21 levels associated with tumor grade of diagnosis and negatively correlated with the median values of patient overall survival time. We further used a lentiviral inhibitor to suppress miR-21 expression in U251 cells. The results showed that the levels of miR-21 target genes of PTEN, RECK and PDCD4 were up-regulated at protein levels. Therefore, we concluded that the exosomal miR-21 levels could be demonstrated as a promising indicator for glioma diagnosis and prognosis, particularly with values to predict tumor recurrence or metastasis.

Keywords: cancer prognosis; cerebrospinal fluid; extracellular vesicles; glioma; hsa-miR-21.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apoptosis Regulatory Proteins / metabolism
  • Astrocytoma / blood
  • Astrocytoma / cerebrospinal fluid
  • Astrocytoma / diagnosis
  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / blood*
  • Brain Neoplasms / cerebrospinal fluid*
  • Brain Neoplasms / diagnosis
  • Cell Line, Tumor
  • Disease Progression
  • Ependymoma / blood
  • Ependymoma / cerebrospinal fluid
  • Ependymoma / diagnosis
  • Exosomes / metabolism*
  • Female
  • GPI-Linked Proteins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / blood
  • Glioblastoma / cerebrospinal fluid
  • Glioblastoma / diagnosis
  • Glioma / blood*
  • Glioma / cerebrospinal fluid*
  • Glioma / diagnosis
  • Humans
  • Kaplan-Meier Estimate
  • Lentivirus / genetics
  • Male
  • MicroRNAs / metabolism*
  • Microscopy, Electron, Transmission
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local
  • PTEN Phosphohydrolase / metabolism
  • Prognosis
  • RNA-Binding Proteins / metabolism
  • ROC Curve
  • Recurrence
  • Time Factors

Substances

  • Apoptosis Regulatory Proteins
  • Biomarkers, Tumor
  • GPI-Linked Proteins
  • MIRN21 microRNA, human
  • MicroRNAs
  • PDCD4 protein, human
  • RECK protein, human
  • RNA-Binding Proteins
  • PTEN Phosphohydrolase
  • PTEN protein, human