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Tac2-N 促进神经胶质瘤增殖并预示不良临床结局。

Tac2-N Promotes Glioma Proliferation and Indicates Poor Clinical Outcomes.

机构信息

Department of Cardiology, Yidu Central Hospital of Weifang.

Department of Neurology, Qingzhou People's Hospital.

出版信息

Tohoku J Exp Med. 2021 Nov;255(3):247-256. doi: 10.1620/tjem.255.247.

DOI:10.1620/tjem.255.247
PMID:34840225
Abstract

As the most common tumor of central nervous system in adults, glioma is characterized with poor prognosis. Tac2-N (TC2N) is a newly discovered protein that play potential roles in lung cancer and breast cancer progression. Here we aimed to investigate the expression, clinical significance, and function of TC2N in glioma. The mRNA level of TC2N in glioma patients was extracted from TCGA datasets. Immunohistochemistry staining was conducted to test protein expression of TC2N in glioma tissues. Chi-square test was used to assess correlations between TC2N expression and patients' clinicopathological characteristics. Kaplan-Meier method was used to plot survival curves. The prognostic predictive role of TC2N was evaluated by univariate and multivariate analyses. Knockdown assays were performed in U87 and U251 cell lines, respectively. Cell proliferation, colony formation, and subcutaneous mice xenografts were used to reveal the tumor-related role of TC2N in glioma. Compared with normal brain tissues, the mRNA level of TC2N was significantly higher in glioma tissues, whose dysregulated higher mRNA level was correlated with poorer overall survival. Similarly, higher protein expression of TC2N was observed in cases with larger tumor size and advanced WHO grades. Univariate and multivariate analyses identified TC2N as a novel independent prognostic factor of gliomas. In vitro and in vivo data demonstrated that TC2N interference can remarkably prevent glioma cell proliferation and tumor growth. In conclusion, high TC2N expression is significantly correlated with poor overall survival of glioma patients via enhancing tumor growth.

摘要

作为成人中枢神经系统最常见的肿瘤,神经胶质瘤的预后较差。Tac2-N(TC2N)是一种新发现的蛋白,在肺癌和乳腺癌的进展中发挥潜在作用。在这里,我们旨在研究 TC2N 在神经胶质瘤中的表达、临床意义和功能。从 TCGA 数据集中提取神经胶质瘤患者的 TC2N mRNA 水平。免疫组织化学染色检测神经胶质瘤组织中 TC2N 蛋白的表达。卡方检验评估 TC2N 表达与患者临床病理特征的相关性。Kaplan-Meier 法绘制生存曲线。单因素和多因素分析评估 TC2N 的预后预测作用。分别在 U87 和 U251 细胞系中进行敲低实验。细胞增殖、集落形成和皮下小鼠异种移植用于揭示 TC2N 在神经胶质瘤中的肿瘤相关作用。与正常脑组织相比,神经胶质瘤组织中 TC2N 的 mRNA 水平明显升高,其失调的高 mRNA 水平与总生存率降低相关。同样,较大肿瘤大小和较高 WHO 分级的病例中观察到 TC2N 蛋白表达较高。单因素和多因素分析均将 TC2N 鉴定为神经胶质瘤的新型独立预后因素。体外和体内数据表明,TC2N 干扰可显著防止神经胶质瘤细胞增殖和肿瘤生长。总之,高 TC2N 表达通过增强肿瘤生长与神经胶质瘤患者的总生存率显著相关。

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