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TRIM28 as an independent prognostic marker plays critical roles in glioma progression

  • Laboratory Investigation
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Abstract

Tripartite motif (TRIM) proteins are involved in tumorigenesis. Here, we examined the expression, biological function, and clinical significance of tripartite motif containing 28 (TRIM28) in glioma, a locally aggressive brain tumor. First, TRIM28 expression was significantly higher in glioma (n = 138) than in non-glioma controls (n = 6). TRIM28 expression was positively correlated with tumor malignancy, and associated with poor overall survival (OS) and progression-free survival (PFS). Notably, TRIM28 expression was negatively correlated with p21 expression in patients with glioblastoma multiforme (GBM). A multivariate analysis that included relevant measures indicated that high TRIM28 expression is an independent prognostic factor for poor OS and PFS in GBM patients. In experiments with cultured glioma cells, down-regulating TRIM28 with shRNA increased p21 expression, and induced cell cycle arrest at the G1 phase. In a xenograft model, down-regulating TRIM28 suppressed tumor growth. These results indicate that over-expression of TRIM28 is associated with poor outcome in glioma patients.

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Abbreviations

TRIM:

Tripartite motif

TRIM28:

Tripartite motif containing 28

OS:

Overall survival

PFS:

Progression-free survival

GBM:

Glioblastoma multiforme

TMA:

Tissue microarray

IHC:

Immunohistochemistry

qRT-PCR:

Quantitative real-time polymerase chain reaction

TCGA:

The Cancer Genome Atlas

MIB-1:

Mind bomb E3 ubiquitin protein ligase 1

KPS:

Karnofsky performance status

MGMT:

O-6-methylguanine-DNA methyltransferase

STR:

Subtotal resection

GTR:

Gross total resection

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Acknowledgments

This work was supported by China National Funds for Distinguished Young Scientists (81025013 to Ying Mao), National Natural and Science Foundation of China (81402053) and International Scientific and Technological Cooperation Projects (2014DFA31470 to Wei Zhu).

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    Authors and Affiliations

    1. Department of Neurosurgery, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai, 200040, China

      Zeng-Xin Qi, Jia-Jun Cai, Ling-Chao Chen, Qi Yue, Yu Yao & Ying Mao

    2. Department of Geriatrics, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai, 200040, China

      Yan Gong

    3. State Key Laboratory of Medical Neurobiology, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China

      Ying Mao

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    1. Zeng-Xin Qi
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    Correspondence to Yan Gong or Yu Yao.

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    Zeng-Xin Qi and Jia-Jun Cai have contributed equally to this work.

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    Qi, ZX., Cai, JJ., Chen, LC. et al. TRIM28 as an independent prognostic marker plays critical roles in glioma progression. J Neurooncol 126, 19–26 (2016). https://doi.org/10.1007/s11060-015-1897-8

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