Identification of miRNA-Mediated Core Gene Module for Glioma Patient Prediction by Integrating High-Throughput miRNA, mRNA Expression and Pathway Structure
机构:[1]Harbin Med Univ, Coll Bioinformat Sci & Technol, Harbin, Peoples R China;[2]Capital Med Univ, Tiantan Hosp, Dept Neurosurg, Beijing, Peoples R China;重点科室诊疗科室神经外科神经外科首都医科大学附属天坛医院[3]Tianjin Med Univ Gen Hosp, Dept Neurosurg, Lab Neurotrauma Variat & Regenerat, Lab Neurooncol,Tianjin Neurol Inst,Minist Educ, Tianjin, Peoples R China;[4]Tianjin Municipal Govt, Tianjin, Peoples R China;[5]Fujian Med Univ, Sch Basic Med Sci, Dept Bioinformat, Fuzhou, Peoples R China
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.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81121003, 61170154, 91129710, 31200996]; National High Technology Research and Development ProgramNational High Technology Research and Development Program of China [2012AA02A508]; International Science and Technology Cooperation Program [2012DFA30470]; Specialized Research Fund for the Doctoral Program of Higher Education of ChinaSpecialized Research Fund for the Doctoral Program of Higher Education (SRFDP) [20102307120027, 20102307110022]
第一作者机构:[1]Harbin Med Univ, Coll Bioinformat Sci & Technol, Harbin, Peoples R China;
通讯作者:
通讯机构:[1]Harbin Med Univ, Coll Bioinformat Sci & Technol, Harbin, Peoples R China;[2]Capital Med Univ, Tiantan Hosp, Dept Neurosurg, Beijing, Peoples R China;
推荐引用方式(GB/T 7714):
Zhang Chunlong,Li Chunquan,Li Jing,et al.Identification of miRNA-Mediated Core Gene Module for Glioma Patient Prediction by Integrating High-Throughput miRNA, mRNA Expression and Pathway Structure[J].PLOS ONE.2014,9(5):-.doi:10.1371/journal.pone.0096908.
APA:
Zhang, Chunlong,Li, Chunquan,Li, Jing,Han, Junwei,Shang, Desi...&Li, Xia.(2014).Identification of miRNA-Mediated Core Gene Module for Glioma Patient Prediction by Integrating High-Throughput miRNA, mRNA Expression and Pathway Structure.PLOS ONE,9,(5)
MLA:
Zhang, Chunlong,et al."Identification of miRNA-Mediated Core Gene Module for Glioma Patient Prediction by Integrating High-Throughput miRNA, mRNA Expression and Pathway Structure".PLOS ONE 9..5(2014):-