Malignant progression of astrocytoma is a multistep process with the integration of genetic abnormalities including grade progression and subtypes transition. Established biomarkers of astrocytomas, like IDH1 and TP53 mutation, were not associated with malignant progression. To identify new biomarker(s) contributing to malignant progression, we collected 252 samples with whole genome mRNA expression profile [34 normal brain tissue (NBT), 136 grade II astrocytoma (AII) and 82 grade III astrocytoma (AIII)]. Bioinformatics analysis revealed that EMT-associated pathways were most significantly altered along with tumor grades progress with up-regulation of 17 genes. Up-regulation of these genes was further confirmed by RNA-sequencing in 128 samples. Survival analysis revealed that high expression of these genes indicates a poor survival outcome. We focused on TGFB1I1 (TGF-beta 1 induced transcript 1) whose expression correlation with WHO grades was further validated by qPCR in 6 cell lines of different grades and 49 independent samples (36 AIIs and 13 AIIIs). High expression of TGFB1I1 was found associated with subtype transition and EMT pathways activation. The conclusion was confirmed using immunohistochemistry in tissue microarrays. Studies in vitro and in vivo using TGF-beta 1 and TGFB1I1 shRNA demonstrated that TGFB1I1 is required for TGF-beta stimulated EMT that contributes to malignant progression of astrocytomas.
基金：
Beijing science and technology plan [Z131100006113018]; National Science Foundation of ChinaNational Natural Science Foundation of China [91229121]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81201993]; Foundation for Beijing Institute of Brain Disorders [BIBD-PXM2013_014226_07_000084]
第一作者机构：[1]Capital Med Univ, Dept Mol Neuropathol, Beijing Neurosurg Inst, Beijing, Peoples R China;[6]CGCG, Beijing, Peoples R China;
通讯作者：
通讯机构：[1]Capital Med Univ, Dept Mol Neuropathol, Beijing Neurosurg Inst, Beijing, Peoples R China;[2]Capital Med Univ, Dept Neurosurg, Beijing Tiantan Hosp, Beijing, Peoples R China;[6]CGCG, Beijing, Peoples R China;[7]China Natl Clin Res Ctr Neurol Dis, Beijing, Peoples R China;[8]Beijing Inst Brain Disorders, Ctr Brain Tumor, Beijing, Peoples R China
推荐引用方式(GB/T 7714)：
Liu Yanwei,Hu Huimin,Wang Kuanyu,et al.Multidimensional analysis of gene expression reveals TGFB1I1-induced EMT contributes to malignant progression of astrocytomas[J].ONCOTARGET.2014,5(24):12593-12606.doi:10.18632/oncotarget.2518.
APA：
Liu, Yanwei,Hu, Huimin,Wang, Kuanyu,Zhang, Chuanbao,Wang, Yinyan...&Jiang, Tao.(2014).Multidimensional analysis of gene expression reveals TGFB1I1-induced EMT contributes to malignant progression of astrocytomas.ONCOTARGET,5,(24)
MLA：
Liu, Yanwei,et al."Multidimensional analysis of gene expression reveals TGFB1I1-induced EMT contributes to malignant progression of astrocytomas".ONCOTARGET 5..24(2014):12593-12606
