机构:[1]Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China研究所北京市神经外科研究所首都医科大学附属天坛医院[2]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China重点科室诊疗科室神经外科神经外科首都医科大学附属天坛医院[3]Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China[4]China National Clinical Research Center for Neurological Diseases, Beijing, China[5]Chinese Glioma Genome Atlas Network (CGGA), Beijing, China
Glioma is the most common primary brain tumor with various genetic alterations; among which, IDH mutation is the most common mutation and plays an important role in glioma early development, especially in lower grade glioma (LGG, WHO II-III). Previous studies have found that IDH mutation is tightly associated with extensive methylation across whole genome in glioma. To further investigate the role of IDH, we obtained methylation data of 777 samples from CGGA (Chinese Glioma Genome Atlas) and TCGA (The Cancer Genome Atlas) with IDH mutation status available. A package compiled under R language called Tspair was used as the main analytic tool to find potential probes that were significantly affected by IDH mutation. As a result, we found one pair of probes, cg06940792 and cg26025891, which was capable of predicting IDH mutation status precisely. The hypermethylated probe was cg06940792, designed in the promoter region of MEGF10, while the hypomethylated probe was cg26025891, designed in the promoter region of PSTPIP1. Survival analysis proved that hypermethylation or low expression of MEGF10 indicated a favorable prognosis in 983 glioma samples. Moreover, gene ontology analysis demonstrated that MEGF10 was associated with cell migration, cell proliferation, and regulation of apoptosis in glioma. All findings above can be validated in three other independent cohorts. In a word, our results suggested that methylation level and mRNA expression of MEGF10 in glioma were not only correlated with IDH mutation but also associated with clinical outcome of patients, providing potential guide for future dissection of IDH role in glioma.
基金:
National Key Research and Development Plan [2016YFC0902500]; Beijing Science and Technology Plan [Z141100000214009]; Capital Medical Development Research Fund [2016-1-1072]; Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support [ZYLX201708]; Jiangsu Province thirteen-five-year science and education project for young people talent [QNRC2016189]; Beijing Nova ProgramBeijing Municipal Science & Technology Commission [Z171100001117022]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81773208, 81672479, 81402052, 81502495, 81702460]
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外文
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出版当年[2017]版:
大类|4 区医学
小类|3 区病理学4 区生物工程与应用微生物4 区遗传学4 区医学:研究与实验
最新[2023]版:
无
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出版当年[2016]版:
Q2BIOTECHNOLOGY & APPLIED MICROBIOLOGYQ2PATHOLOGYQ3GENETICS & HEREDITYQ3MEDICINE, RESEARCH & EXPERIMENTAL
第一作者机构:[1]Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China[2]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
共同第一作者:
通讯作者:
通讯机构:[1]Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China[2]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China[3]Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China[4]China National Clinical Research Center for Neurological Diseases, Beijing, China[5]Chinese Glioma Genome Atlas Network (CGGA), Beijing, China
推荐引用方式(GB/T 7714):
Li Guanzhang,Wang Zhiliang,Zhang Chuanbao,et al.MEGF10, a Glioma Survival-Associated Molecular Signature, Predicts IDH Mutation Status[J].DISEASE MARKERS.2018,2018:-.doi:10.1155/2018/5975216.