title: Identification of miRNA-mediated core gene module for glioma patient prediction by integrating high-throughput miRNA, mRNA expression and pathway structure.
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.
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Chunlong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Chunquan
authors.initials: C
authors.lastname: Li
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China; Department of Bioinformatics, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Han
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Desi
authors.initials: D
authors.lastname: Shang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Qianlan
authors.initials: Q
authors.lastname: Yao
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Neurosurgery, Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: Zhaoshi
authors.initials: Z
authors.lastname: Bao
authors.affiliation: Department of Neurosurgery, Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: Gan
authors.initials: G
authors.lastname: You
authors.affiliation: Department of Neurosurgery, Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin, China.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Kang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
mesh_terms: D000328:Adult; D019295:Computational Biology / Q000379:methods*; D005260:Female; D020869:Gene Expression Profiling; D052138:Genes, Neoplasm / Q000235:genetics*; D005910:Glioma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D060787:Neoplasm Grading; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction; D016019:Survival Analysis
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger