Identification of miRNA-mediated core gene module for glioma patient prediction by integrating high-throughput miRNA, mRNA expression and pathway structure

PLoS One. 2014 May 8;9(5):e96908. doi: 10.1371/journal.pone.0096908. eCollection 2014.

Abstract

The prognosis of glioma patients is usually poor, especially in patients with glioblastoma (World Health Organization (WHO) grade IV). The regulatory functions of microRNA (miRNA) on genes have important implications in glioma cell survival. However, there are not many studies that have investigated glioma survival by integrating miRNAs and genes while also considering pathway structure. In this study, we performed sample-matched miRNA and mRNA expression profilings to systematically analyze glioma patient survival. During this analytical process, we developed pathway-based random walk to identify a glioma core miRNA-gene module, simultaneously considering pathway structure information and multi-level involvement of miRNAs and genes. The core miRNA-gene module we identified was comprised of four apparent sub-modules; all four sub-modules displayed a significant correlation with patient survival in the testing set (P-values≤0.001). Notably, one sub-module that consisted of 6 miRNAs and 26 genes also correlated with survival time in the high-grade subgroup (WHO grade III and IV), P-value = 0.0062. Furthermore, the 26-gene expression signature from this sub-module had robust predictive power in four independent, publicly available glioma datasets. Our findings suggested that the expression signatures, which were identified by integration of miRNA and gene level, were closely associated with overall survival among the glioma patients with various grades.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Computational Biology / methods*
  • Female
  • Gene Expression Profiling*
  • Genes, Neoplasm / genetics*
  • Glioma / diagnosis
  • Glioma / genetics*
  • Glioma / pathology*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Neoplasm Grading
  • Prognosis
  • RNA, Messenger / genetics
  • Signal Transduction*
  • Survival Analysis

Substances

  • MicroRNAs
  • RNA, Messenger

Grant support

This work was supported by the National Natural Science Foundation of China (Grant Nos. 81121003), the National Natural Science Foundation of China (Grant Nos. 61170154, 91129710 and 31200996), the National High Technology Research and Development Program (No. 2012AA02A508), the International Science and Technology Cooperation Program (No. 2012DFA30470) and the Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant Nos. 20102307120027 and 20102307110022). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.