Predictive and Prognostic Roles of Abnormal Expression of Tissue miR-125b, miR-221, and miR-222 in Glioma

Mol Neurobiol. 2016 Jan;53(1):577-583. doi: 10.1007/s12035-014-9017-x. Epub 2014 Dec 11.

Abstract

Glioma is the most prevalent primary brain tumors in adults. In addition to the high incidence and mortality rate, the 5-year survival rate of glioma is also extremely low. MicroRNAs (miRNAs), as a class of small non-coding RNAs, may play an important role in carcinogenesis. It was also proposed that miRNAs might also be associated with glioma diagnosis and prognosis. In this study, we aimed at investigating the predictive and prognostic values of miR-125b, miR-221, and miR-222 in glioma and, hopefully, to provide some evidence for novel therapy of glioma. Tissue specimens were obtained from tumor tissue and adjacent non-tumor tissue. RNA was extracted and qRT-PCR was performed with U6 being the internal control. Receiver-operating characteristic (ROC) curves were constructed, and the area under the ROC curves (AUC) was calculated to evaluate the significance of candidate miRNAs in distinguishing glioma tumor tissues and adjacent normal tissues. Survival curves of Kaplan-Meier method were constructed for both high expression group and low expression group, and the difference between curves was evaluated by log-rank test. All the statistical analyses were performed using Stata version 12.0 software, and graphs were generated by GraphPad Prism 5.0. The significance of miR-125b, miR-221, and miR-222 expression level in distinguishing glioma tumor from adjacent non-tumor tissues was further validated. Combination of miR-125b, miR-221, and miR-22 was significantly superior compared to the clinical standard of using these miRNAs alone. A clear demarcation was shown by survival analysis between patients with high miR-125b, miR-221, and miR-222 expression and patients with poor prognosis. Similarly, panel of these miRNAs could play a better prognostic role in glioma. In this study, we confirmed the significance of miR-125b, miR-221, and miR-222 in distinguishing glioma tumor from adjacent non-tumor tissues. Higher expressions of miR-125b and miR-222 have also been proved to be associated with glioma. Furthermore, glioma patients with higher miR-125b, miR-221, and miR-222 expression were manifested to have poorer prognostic status, which might be attributed to their attenuated sensitivity to chemotherapy and radiotherapy.

Keywords: Diagnosis; Glioma; Prognosis; Tissue; miR-125b; miR-221; miR-222.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Glioma / diagnosis
  • Glioma / genetics
  • Glioma / metabolism*
  • Humans
  • Male
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis

Substances

  • Biomarkers, Tumor
  • MIRN125 microRNA, human
  • MIRN221 microRNA, human
  • MIRN222 microRNA, human
  • MicroRNAs