Co-expression of mitosis-regulating genes contributes to malignant progression and prognosis in oligodendrogliomas
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Yanwei Liu1,2,5, Huimin Hu1,5, Chuanbao Zhang1,5, Haoyuan Wang3, Wenlong Zhang2, Zheng Wang1,5, Mingyang Li1,5, Wei Zhang1,2,5,6, Dabiao Zhou2,5, Tao Jiang1,2,4,5,6
1Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
2Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
3Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
4Brain Tumor Center, Beijing Institute for Brain Disorders, Beijing, China
5Chinese Glioma Cooperative Group (CGCG), China
6National Clinical Research Center for Neurological Diseases, Beijing, China
Tao Jiang, e-mail: firstname.lastname@example.org
Dabiao Zhou, e-mail: email@example.com
Keywords: oligodendrogliomas, prognosis, malignant progression, proliferation, gene expression
Received: June 30, 2015 Accepted: September 30, 2015 Published: October 12, 2015
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.
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