Abstract
AimThis 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.MethodWe 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.ResultWe 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.ConclusionThe 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.
Highlights
Among primary central nervous system tumors, gliomas are the largest and most diverse group [1]
Result: We observed that 11,795 DNA methylation sites, 3,627 genes, 136 microRNAs, and 3,334 long non-coding RNA (lncRNA) were significantly differential between tumors and non-tumor brain tissues, and the filtered signatures through comprehensive analysis were significantly enriched in calcium signaling pathway
The calcium signaling pathway played a key role in astrocytoma tumorigenesis and prognosis
Summary
Among primary central nervous system tumors, gliomas are the largest and most diverse group [1]. Gliomas can be classified as astrocytomas, oligodendrogliomas or oligoastrocytomas and graded as I to IV according to the histopathological classification of World Health Organization [2]. The single traditional diagnostic method based on histopathologic characteristics cannot satisfy the requirement of predicting clinical outcomes [4,5,6]. Understanding of genetic biomarker has been improved along with the discovery of numerous molecular alterations in gliomas. Some molecular alterations are recognized as major biomarkers of clinical behavior and molecular classification, including IDH mutation, 1p/19q codeletion, TERT mutation and MGMT methylation [7,8,9,10,11,12,13]. The genetic and epigenetic characteristics of astrocytomas have not been extensively explored by multiplatform comprehensive analysis
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