The molecular classification of astrocytic tumors
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Chen-Xue Mao1,3, Ji-Ye Yin1,3, Ying Zhang1,3, Zhi-Bin Wang1,3, Zhi-Quan Yang2, Zheng-Wen He4, Xiang-Min Li5, Xiao-Yuan Mao1,3, Ru-Tao Cui6, Xue-Jun Li2, Xi Li1,3, Wei Zhang1,3, Hong-Hao Zhou1,3 and Zhao-Qian Liu1,3
1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China
2Department Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, P. R. China
3Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China
4Department of Neurosurgery, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410014, P. R. China
5Department of Emergency, Xiangya Hospital, Central South University, Changsha 410008, P. R. China
6Departments of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, USA
Zhao-Qian Liu, email: [email protected]
Keywords: astrocytoma, calcium signaling pathway, IDH, molecular classification, chemokine signaling pathway
Received: July 29, 2017 Accepted: August 23, 2017 Published: October 25, 2017
Aim: This study will explore the genetic and epigenetic alterations in astrocytomas, and identify the critical molecular signatures and signaling pathways for prognosis assessment by multiplatform comprehensive analysis.
Method: We performed integration analyses of incorporating DNA methylation, mRNA expression, microRNA expression, and long non-coding RNA (lncRNA) expression in 33 astrocytic tumor tissues and 9 non-tumor brain tissues.
Result: We observed that 11,795 DNA methylation sites, 3,627 genes, 136 microRNAs, and 3,334 lncRNAs were significantly differential between tumors and non-tumor brain tissues, and the filtered signatures through comprehensive analysis were significantly enriched in calcium signaling pathway. Furthermore, four signatures involved in calcium signaling pathway and age could contribute to predicting the patients’ overall survival. Additionally, we identified differentially expressed signatures between IDH-mutated and IDH wild-type astrocytic tumors, and complement and coagulation cascades pathway was the most significant pathway in functional enrichment analysis using multiplatform data. The IDH wild-type astrocytomas were divided into two subtypes by Cluster of Cluster (CoC) analysis, one of which was enriched for astrocytomas overexpressed in chemokine signaling pathway.
Conclusion: The calcium signaling pathway played a key role in astrocytoma tumorigenesis and prognosis. IDH mutation was a vital biomarker, and resulted in the change of expression level in complement and coagulation cascades pathway. The chemokine signaling pathway could characterize subtypes of IDH wild-type astrocytomas.
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