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Multidimensional analysis of gene expression reveals TGFB1I1-induced EMT contributes to malignant progression of astrocytomas

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 biomarke...

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Autores principales: Liu, Yanwei, Hu, Huimin, Wang, Kuanyu, Zhang, Chuanbao, Wang, Yinyan, Yao, Kun, Yang, Pei, Han, Lei, Kang, Chunsheng, Zhang, Wei, Jiang, Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350345/
https://www.ncbi.nlm.nih.gov/pubmed/25333259
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author Liu, Yanwei
Hu, Huimin
Wang, Kuanyu
Zhang, Chuanbao
Wang, Yinyan
Yao, Kun
Yang, Pei
Han, Lei
Kang, Chunsheng
Zhang, Wei
Jiang, Tao
author_facet Liu, Yanwei
Hu, Huimin
Wang, Kuanyu
Zhang, Chuanbao
Wang, Yinyan
Yao, Kun
Yang, Pei
Han, Lei
Kang, Chunsheng
Zhang, Wei
Jiang, Tao
author_sort Liu, Yanwei
collection PubMed
description 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-β1 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-β1 and TGFB1I1 shRNA demonstrated that TGFB1I1 is required for TGF-β stimulated EMT that contributes to malignant progression of astrocytomas.
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spelling pubmed-43503452015-03-06 Multidimensional analysis of gene expression reveals TGFB1I1-induced EMT contributes to malignant progression of astrocytomas Liu, Yanwei Hu, Huimin Wang, Kuanyu Zhang, Chuanbao Wang, Yinyan Yao, Kun Yang, Pei Han, Lei Kang, Chunsheng Zhang, Wei Jiang, Tao Oncotarget Research Paper 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-β1 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-β1 and TGFB1I1 shRNA demonstrated that TGFB1I1 is required for TGF-β stimulated EMT that contributes to malignant progression of astrocytomas. Impact Journals LLC 2014-12-31 /pmc/articles/PMC4350345/ /pubmed/25333259 Text en Copyright: © 2014 Liu et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Liu, Yanwei
Hu, Huimin
Wang, Kuanyu
Zhang, Chuanbao
Wang, Yinyan
Yao, Kun
Yang, Pei
Han, Lei
Kang, Chunsheng
Zhang, Wei
Jiang, Tao
Multidimensional analysis of gene expression reveals TGFB1I1-induced EMT contributes to malignant progression of astrocytomas
title Multidimensional analysis of gene expression reveals TGFB1I1-induced EMT contributes to malignant progression of astrocytomas
title_full Multidimensional analysis of gene expression reveals TGFB1I1-induced EMT contributes to malignant progression of astrocytomas
title_fullStr Multidimensional analysis of gene expression reveals TGFB1I1-induced EMT contributes to malignant progression of astrocytomas
title_full_unstemmed Multidimensional analysis of gene expression reveals TGFB1I1-induced EMT contributes to malignant progression of astrocytomas
title_short Multidimensional analysis of gene expression reveals TGFB1I1-induced EMT contributes to malignant progression of astrocytomas
title_sort multidimensional analysis of gene expression reveals tgfb1i1-induced emt contributes to malignant progression of astrocytomas
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350345/
https://www.ncbi.nlm.nih.gov/pubmed/25333259
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