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Talin-1的高表达与鼻咽癌患者的不良预后相关。

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

作者信息

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

机构信息

State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, People's Republic of China.

出版信息

BMC Cancer. 2015 Apr 30;15:332. doi: 10.1186/s12885-015-1351-5.

DOI:10.1186/s12885-015-1351-5
PMID:25925041
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4424526/
Abstract

BACKGROUND

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).

METHODS

Talin-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.

RESULTS

The 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.

CONCLUSIONS

Our 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.

摘要

背景

踝蛋白-1是一种细胞骨架蛋白，在多种恶性肿瘤的肿瘤发生、迁移和转移中起重要作用。本研究旨在评估踝蛋白-1在鼻咽癌（NPC）中的表达及预后价值。

方法

采用定量逆转录聚合酶链反应（RT-PCR）、琼脂糖凝胶电泳和蛋白质免疫印迹法检测NPC细胞系和临床鼻咽癌组织中踝蛋白-1 mRNA和蛋白的表达。通过免疫组织化学染色分析233例有临床随访数据的石蜡包埋NPC标本中踝蛋白-1的表达，并采用Cox回归分析确定独立预后因素。通过小干扰RNA介导的蛋白缺失，随后进行伤口愈合和Transwell侵袭试验，评估踝蛋白-1在NPC细胞系中的功能作用。

结果

在大多数NPC细胞系和临床组织中，踝蛋白-1在mRNA和蛋白水平均显著上调。踝蛋白-1高表达与远处转移（P = 0.001）和患者死亡（P = 0.001）显著相关。此外，踝蛋白-1高表达与总体生存率显著降低（OS：风险比[HR]，2.15；95%置信区间[CI]，1.28 - 3.63；P = 0.003）和远处无转移生存率降低（DMFS：HR，2.39；95% CI，1.38 - 4.15；P = 0.001）相关。Cox回归分析表明，踝蛋白-1高表达和TNM分期是独立的预后指标（均P < 0.05）。分层分析表明，踝蛋白-1高表达与晚期疾病患者（III - IV期）生存率显著降低相关（OS：HR，1.91；95% CI，1.09 - 3.35；P = 0.02；DMFS：HR，2.22；95% CI，1.24 - 3.99；P = 0.006）。此外，踝蛋白-1缺失抑制了NPC细胞在体外的迁移和侵袭能力。

结论

我们的数据表明，踝蛋白-1高表达与NPC患者的OS显著降低和DMFS降低相关，踝蛋白-1表达缺失抑制了NPC细胞的迁移和侵袭。踝蛋白-1可能是NPC中的一种新型预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6921/4424526/09420c4ffcca/12885_2015_1351_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6921/4424526/b5c363cbff59/12885_2015_1351_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6921/4424526/1fa00ec5d76b/12885_2015_1351_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6921/4424526/9973dfb1ebff/12885_2015_1351_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6921/4424526/f3973973aee5/12885_2015_1351_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6921/4424526/09420c4ffcca/12885_2015_1351_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6921/4424526/b5c363cbff59/12885_2015_1351_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6921/4424526/1fa00ec5d76b/12885_2015_1351_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6921/4424526/9973dfb1ebff/12885_2015_1351_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6921/4424526/f3973973aee5/12885_2015_1351_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6921/4424526/09420c4ffcca/12885_2015_1351_Fig5_HTML.jpg

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