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TWAl 的过表达预示着胃癌患者的预后不良。

Overexpression of TWA1 predicts poor prognosis in patients with gastric cancer.

机构信息

Department of Gastrointestinal Surgery, the First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China.

Department of Gastrointestinal Surgery, the First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China.

出版信息

Pathol Res Pract. 2019 Nov;215(11):152594. doi: 10.1016/j.prp.2019.152594. Epub 2019 Aug 16.

Abstract

TWA1 is associated with microtubule dynamics, cell migration, nucleokinesis and chromosome segregation. However, the role of TWA1 in gastric cancer (GC) remains unclear. In this study, Cosmic database revealed that the expression level of TWA1 ranks in the top 20 of overexpressed genes in GC. Further bioinformatic analysis revealed that the expression level of TWA1 was not in connection with the infection status of HP or EB. IHC and IF showed that TWA1 protein was present in both the cytoplasm and nucleus, but mainly in the cytoplasm. The high expression level of TWA1 was also related to tumor size, depth of invasion, lymph node metastasis, TNM stage, cancerous node and vascular invasion. Furthermore, higher TWA1 expression was also associated with shorter PFS and OS in GC. The univariate and multivariate analysis suggested the expression of TWA1 was an independent poor prognostic factor in GC. DNA copy number gain contributes to TWA1 overexpression and promoter methylation of TWA1 predicts profitable prognosis. Co-expression showed that TAF4 may function as a transcription factor (TF) regulates TWA1 expression, which further to mediate tumor invasion and metastasis. These findings revealed that TWA1 plays an important role in the development of GC and is expected to become an important biomarker and therapeutic target of tumors.

摘要

TWA1 与微管动力学、细胞迁移、核分裂和染色体分离有关。然而,TWA1 在胃癌(GC)中的作用尚不清楚。在这项研究中,Cosmic 数据库显示 TWA1 的表达水平在 GC 中过表达基因的前 20 名之列。进一步的生物信息学分析显示,TWA1 的表达水平与 HP 或 EB 的感染状态无关。免疫组化和免疫荧光显示 TWA1 蛋白存在于细胞质和细胞核中,但主要存在于细胞质中。TWA1 的高表达水平也与肿瘤大小、浸润深度、淋巴结转移、TNM 分期、癌性淋巴结和血管侵犯有关。此外,GC 中 TWA1 表达水平较高与较短的 PFS 和 OS 相关。单因素和多因素分析表明,TWA1 的表达是 GC 的独立不良预后因素。DNA 拷贝数增加导致 TWA1 过表达,TWA1 启动子甲基化预测有利的预后。共表达表明 TAF4 可能作为转录因子(TF)调节 TWA1 的表达,进而介导肿瘤的侵袭和转移。这些发现表明 TWA1 在 GC 的发展中起着重要作用,有望成为肿瘤的重要生物标志物和治疗靶点。

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