High expression of Talin-1 is associated with poor prognosis in patients with nasopharyngeal carcinoma.

Ya-Fei Xu,Jian-Yong Shao,Ying Sun,Wei-Hua Jia,Jun Ma,Tie-Bang Kang,Xian-Yue Ren,Qing-Mei He,Ying-Qin Li,Na Liu,Mu-Sheng Zeng,Xin-Ran Tang

doi:10.1186/s12885-015-1351-5

Ya-Fei Xu, Jian-Yong Shao + Show 10 more

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https://doi.org/10.1186/s12885-015-1351-5

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Abstract

BackgroundTalin-1 is a cytoskeletal protein that plays an important role in tumourgenesis, migration and metastasis in several malignant tumors. The aim of this study was to evaluate the expression and prognostic value of Talin-1 in nasopharyngeal carcinoma (NPC).MethodsTalin-1 mRNA and protein expression were examined in NPC cell lines and clinical nasopharyngeal tissues by quantitative RT-PCR, agarose gel electrophoresis and western blotting. The expression of Talin-1 was analyzed by immunohistochemical staining in 233 paraffin-embedded NPC specimens with clinical follow-up data and cox regression analysis was used to identify independent prognostic factors. The functional role of Talin-1 in NPC cell lines was evaluated by small interfering RNA-mediated depletion of the protein followed by the wound healing and transwell invasion assays.ResultsThe expression of Talin-1 was significantly upregulated in most NPC cell lines and clinical tissues at both the mRNA and protein levels. High expression of Talin-1 was significantly associated with distant metastasis (P = 0.001) and patient death (P = 0.001). In addition, high expression of Talin-1 was associated with significantly poorer overall survival (OS: HR, 2.15; 95% CI, 1.28-3.63; P = 0.003) and poorer distant metastasis-free survival (DMFS: HR, 2.39; 95% CI, 1.38-4.15; P = 0.001). Cox regression analysis indicated that high expression of Talin-1 and TNM stage were independent prognostic indicators (both P < 0.05). Stratified analysis demonstrated that high expression of Talin-1 was associated with significantly poorer survival in patients with advanced stage disease (stage III-IV, HR, 1.91; 95% CI, 1.09-3.35; P = 0.02 for OS and HR, 2.22; 95% CI, 1.24-3.99; P = 0.006 for DMFS). Furthermore, the depletion of Talin-1 suppressed the migratory and invasive ability of NPC cells in vitro.ConclusionsOur data demonstrate that high expression of Talin-1 is associated with significantly poorer OS and poorer DMFS in NPC and depletion of Talin-1 expression inhibited NPC cell migration and invasion. Talin-1 may serve as novel prognostic biomarker in NPC.

Highlights

Talin-1 is a cytoskeletal protein that plays an important role in tumourgenesis, migration and metastasis in several malignant tumors
Talin-1 is upregulated in nasopharyngeal carcinoma (NPC) cells and tissues The mRNA and protein expression levels of Talin-1 in the normal nasopharyngeal epithelial cell line NP69 and NPC cell lines were assessed by quantitative RT-PCR, agarose gel electrophoresis and Western blot analysis
Compared to NP69 cells, Talin-1 was significantly upregulated in all NPC cell lines tested at both the mRNA and protein levels, except for HNE1 cells (Figure 1A, C, E)

Summary

Introduction

Talin-1 is a cytoskeletal protein that plays an important role in tumourgenesis, migration and metastasis in several malignant tumors. The aim of this study was to evaluate the expression and prognostic value of Talin-1 in nasopharyngeal carcinoma (NPC). The clinical TNM (tumor, node, metastasis) staging system for NPC is most frequently used to estimate prognosis. Several molecular biomarkers have been identified to be associated with prognosis in NPC, such as breast cancer metastasis suppressor 1 (BRMS1), metastasis-associated protein 1 (MTA1), Dicer 11, centromere protein-H (CENP-H) and cancerous inhibitor of protein phosphatase 2A (CIP2A) [9,10,11,12,13]; prognostic prediction in NPC remains extremely poor [14].

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