Expression and prognostic significance of TCTN1 in human glioblastoma

Journal of Translational Medicine

Daru Lu¹  Hongyan Chen¹  Juxiang Chen³  Song Yang²  Dapeng Yun¹  Jingkun Wang¹  Yingjie Zhao¹  Yuanyuan Chen¹  Delong Meng¹ 

[1] State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, No. 2005 Songhu Road, Shanghai 200438, People¿s Republic of China;The Eighth Department of General Surgery and Department of Pathology, the First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, People¿s Republic of China;Department of Neurosurgery, Shanghai Institute of Neurosurgery, Changzheng Hospital, Second Military Medical University, No. 415 Fengyang Road, Shanghai 200003, People¿s Republic of China

关键词: Prognostic factor;    Survival;    Glioblastoma;    TCTN1;   

Others  :  1147685
DOI  :  10.1186/s12967-014-0288-9

 received in 2014-07-17, accepted in 2014-10-03,  发布年份 2014

【 摘 要 】

Background

Glioblastoma (GBM) is the most common and lethal intracranial malignancy in adults, with dismal prognosis despite multimodal therapies. Tectonic family member 1 (TCTN1) is a protein involved in a diverse range of developmental processes, yet its functions in GBM remain unclear. This study aims to investigate expression profile, prognostic value and effects of TCTN1 gene in GBM.

Methods

Protein levels of TCTN1 were assessed by immunohistochemical staining using a tissue microarray constructed by a Chinese cohort of GBM patients (n?=?110), and its mRNA expression was also detected in a subset of this cohort. Kaplan-Meier analysis and Cox regression were performed to estimate the prognostic significance of TCTN1. Similar analyses were also conducted in another two independent cohorts: The Cancer Genome Atlas (TCGA) cohort (n?=?528) and the Repository for Molecular Brain Neoplasia Data (REMBRANDT) cohort (n?=?228). For the TCGA cohort, the relationships between TCTN1 expression, clinical outcome, molecular subtypes and genetic alterations were also analysed. Furthermore, proliferation of TCTN1 overexpressed or silenced GBM cells was determined by CCK-8 assays.

Results

As discovered in three independent cohorts, both mRNA and protein levels of TCTN1 expression were markedly elevated in human GBMs, and higher TCTN1 expression served as an independent prognostic factor predicting poorer prognosis of GBM patients. Additionally, in the TCGA cohort, TCTN1 expression was dramatically decreased in patients within the proneural subtype compared to other subtypes, and significantly influenced by the status of several genetic aberrations such as CDKN2A/B deletion, EGFR amplification, PTEN deletion and TP53 mutation. The prognostic value of TCTN1 was more pronounced in proneural and mesenchymal subtypes, and was also affected by several genetic alterations particularly PTEN deletion. Furthermore, overexpression of TCTN1 significantly promoted proliferation of GBM cells, while its depletion evidently hampered cell growth.

Conclusions

TCTN1 is elevated in human GBMs and predicts poor clinical outcome for GBM patients, which is associated with molecular subtypes and genetic features of GBMs. Additionally, TCTN1 expression impacts GBM cell proliferation. Our results suggest for the first time that TCTN1 may serve as a novel prognostic factor and a potential therapeutic target for GBM.

【 授权许可】

   
2014 Meng et al.; licensee BioMed Central Ltd.

【 图 表 】

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