title: Co-expression of mitosis-regulating genes contributes to malignant progression and prognosis in oligodendrogliomas.
abstract: The clinical prognosis of patients with glioma is determined by tumor grades, but tumors of different subtypes with equal malignancy grade usually have different prognosis that is largely determined by genetic abnormalities. Oligodendrogliomas (ODs) are the second most common type of gliomas. In this study, integrative analyses found that distribution of TCGA transcriptomic subtypes was associated with grade progression in ODs. To identify critical gene(s) associated with tumor grades and TCGA subtypes, we analyzed 34 normal brain tissue (NBT), 146 WHO grade II and 130 grade III ODs by microarray and RNA sequencing, and identified a co-expression network of six genes (AURKA, NDC80, CENPK, KIAA0101, TIMELESS and MELK) that was associated with tumor grades and TCGA subtypes as well as Ki-67 expression. Validation of the six genes was performed by qPCR in additional 28 ODs. Importantly, these genes also were validated in four high-grade recurrent gliomas and the initial lower-grade gliomas resected from the same patients. Finally, the RNA data on two genes with the highest discrimination potential (AURKA and NDC80) and Ki-67 were validated on an independent cohort (5 NBTs and 86 ODs) by immunohistochemistry. Knockdown of AURKA and NDC80 by siRNAs suppressed Ki-67 expression and proliferation of gliomas cells. Survival analysis showed that high expression of the six genes corporately indicated a poor survival outcome. Correlation and protein interaction analysis provided further evidence for this co-expression network. These data suggest that the co-expression of the six mitosis-regulating genes was associated with malignant progression and prognosis in ODs.
authors.affiliation: Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), China.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), China.
authors.forename: Chuanbao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Haoyuan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), China.
authors.forename: Mingyang
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), China.|National Clinical Research Center for Neurological Diseases, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), China.
authors.forename: Dabiao
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Brain Tumor Center, Beijing Institute for Brain Disorders, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), China.|National Clinical Research Center for Neurological Diseases, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
mesh_terms: D064096:Aurora Kinase A / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019295:Computational Biology; D030541:Databases, Genetic; D018450:Disease Progression; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008938:Mitosis / Q000235:genetics*; D060787:Neoplasm Grading; D009837:Oligodendroglioma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D060066:Protein Interaction Maps; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019394:Ki-67 Antigen; C576917:AURKA protein, human; D064096:Aurora Kinase A
keywords: gene expression; malignant progression; oligodendrogliomas; prognosis; proliferation