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Transforming growth factor beta induced (TGFBI) is a potential signature gene for mesenchymal subtype high-grade glioma

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Abstract

Previous study revealed that higher expression of transforming growth factor beta induced (TGFBI) is correlated to poorer cancer-specific survival and higher proportion of tumor necrosis and Fuhrman grades III and IV in clear cell renal cell carcinomas. However, the relationships between TGFBI expression and malignant phenotypes of gliomas remain unclear. We downloaded and analyzed data from seven GEO datasets (GSE68848, GSE4290, GSE13041, GSE4271, GSE83300, GSE34824 and GSE84010), the TCGA database and the REMBRANDT database to investigate whether TGFBI could be a biomarker of glioma. From microarray data (GSE68848, GSE4290) and RNA-seq data (TCGA), TGFBI expression levels were observed to correlate positively with pathological grade, and TGFBI expression levels were significantly higher in gliomas than in normal brain tissues. Furthermore, in GSE13041, GSE4271 and the TCGA cohort, TGFBI expression in the mesenchymal (Mes) subtype high-grade glioma (HGG) was significantly higher than that in the proneural subtype. Kaplan–Meier survival analysis of GBM patients in the GSE83300 dataset, REMBRANDT and TCGA cohort revealed that patients in the top 50% TGFBI expression group survived for markedly shorter periods than those in the bottom 50%. Analysis of grade III gliomas showed that the median survival time was significantly shorter in the TGFBI high expression group than in the TGFBI low expression group. In addition, we found that TGFBI expression levels might relate to several classical molecular characterizations of glioma, such as, IDH mutation, TP53 mutation, EGFR amplification, etc. These results suggest that TGFBI expression positively correlates with glioma pathological grades and that TGFBI is a potential signature gene for Mes subtype HGG and a potential prognostic molecule.

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Acknowledgements

We would like to express our thanks to National Library of Medicine for giving user the privilege to freely download the raw data of various GEO series. We would like to thank the TCGA and REMBRANDT database for providing raw data with a large amount of clinical information.

Funding

This study was supported by the Key Program from the Ministry of Science and Technology of China (2016YFC0106104).

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Author notes

  1. Yuan-Bo Pan, Chi-Hao Zhang and Si-Qi Wang are co-first author.

Authors and Affiliations

  1. Department of Neurosurgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201999, China

    Yuan-Bo Pan, Kui Chen, Liang Zhu, Zhao-Liang Sun & Dong-Fu Feng

  2. Department of General Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201999, China

    Chi-Hao Zhang

  3. Department of Radiology, Affiliated Hospital of Medical School of Ningbo University, Ningbo, 315020, Zhejiang Province, China

    Si-Qi Wang

  4. Department of Neurology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China

    Peng-Hui Ai

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Correspondence to Dong-Fu Feng.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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As personal identifying information was not included in the REMBRANDT database and TCGA database, thus the informed consent was not required in this study.

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11060_2017_2729_MOESM3_ESM.tiff

Supplementary material 3—Overall survival curves of grade II and III astrocytoma/ODG patients from REMBRADNT cohort based on TGFBI expression level. a-d. Different histological subtypes (astrocytoma and ODG) of grade III/II glioma patients were divided into top 50% and bottom 50% expression groups according to TGFBI expression levels. Kaplan-Meier survival curves for the top 50% expression group and bottom 50% expression group. a. In grade III astrocytoma, the median survival time was shorter in the high TGFBI expression group (n=19) (20.1 months) than in the low TGFBI expression group (n=19) (42.53 months, p=0. 3266). b. Top 50% group (n=10) in grade III ODG patients from REMBRANDT cohort had a significantly shorter median survival period than low 50% group (n=10) (11.33 months vs 61.72 months, p=0.0071). c. There was no significant difference of median survival time between top 50% (n=22) and low 50% (n=22) groups of grade II astrocytomas (65.13 months vs 68.3 months, p=0.3992). d. There was no significant difference of median survival period between high 50% (n=8) and low 50% (n=8) groups of grade II ODGs (45.3 months vs 42.8 months, p=0.6214) (TIFF 9 KB)

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Pan, YB., Zhang, CH., Wang, SQ. et al. Transforming growth factor beta induced (TGFBI) is a potential signature gene for mesenchymal subtype high-grade glioma. J Neurooncol 137, 395–407 (2018). https://doi.org/10.1007/s11060-017-2729-9

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