Overexpression of TWA1 predicts poor prognosis in patients with gastric cancer
Overexpression of TWA1 predicts poor prognosis in patients with gastric cancer
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TWA1过度表达预示胃癌患者预后不良
DOI：
10.1016/j.prp.2019.152594
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发表时间：
2019-01-01
影响因子：
2.8
通讯作者：
Cao, Yi
中科院分区：
文献类型：
--
作者：
Xiong, Jianbo;Feng, Zongfeng;Cao, Yi
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) 中的作用仍不清楚。本研究中，Cosmic数据库显示，TWA1的表达量位居GC中过表达基因的前20名。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。 IHC和IF显示TWA1蛋白同时存在于细胞质和细胞核中，但主要存在于细胞质中。 TWA1的高表达还与肿瘤大小、浸润深度、淋巴结转移、TNM分期、癌结节和血管侵犯有关。此外，较高的 TWA1 表达还与 GC 中较短的 PFS 和 OS 相关。单变量和多变量分析表明TWA1的表达是GC的独立不良预后因素。 DNA 拷贝数增加导致 TWA1 过度表达，TWA1 启动子甲基化可预测有利的预后。共表达表明TAF4可能作为转录因子（TF）调节TWA1表达，进一步介导肿瘤侵袭和转移。这些发现揭示了TWA1在GC的发生发展中发挥着重要作用，有望成为肿瘤的重要生物标志物和治疗靶点。
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.