Expression and prognostic significance of TCTN1 in human glioblastoma

Abstract

Doc number: 288

Abstract

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.