High Expression of TRIM15 Is Associated with Tumor Invasion and Predicts Poor Prognosis in Patients with Gastric Cancer

High Expression of TRIM15 Is Associated with Tumor Invasion and Predicts Poor Prognosis in Patients with Gastric Cancer
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TRIM15的高表达与肿瘤侵袭相关并预示着胃癌患者的不良预后

DOI:
10.1080/08941939.2019.1705443
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发表时间:
2020-01
影响因子:
1.9
通讯作者:
Liu Fenglin
Liu Fenglin
中科院分区:
医学4区
文献类型:
--
作者:
Zhou Weiran;Chen Hao;Ruan Yuanyuan;Zeng Xiaoqing;Liu Fenglin

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摘要背景胃癌是世界范围内第三大癌症相关死亡原因。大多数三肽基序(TRIM)家族蛋白被称为E3泛素连接酶,相当多的先前研究已经揭示了TRIM蛋白在致癌作用中的参与。TRIM 15是TRIM家族的一种蛋白质,本研究的目的是研究TRIM 15在胃癌中的作用。方法应用免疫组织化学方法检测复旦大学附属中山医院肿瘤标本中TRIM 15的表达。我们还用胃癌细胞进行了transwell实验和western blot实验。结果TRIM 15在胃癌组织中的表达高于正常组织。TRIM 15高表达与胃癌浸润深度(P = 0.007)、淋巴结转移(P = 0.013)、远处转移(P = 0.031)、TNM分期(P = 0.002)及总生存期(P < 0.001)均呈正相关。值得一提的是,TRIM 15是OS的一个不良预后变量。为了获得更多的了解,我们将TRIM 15表达纳入肿瘤淋巴结转移(TNM)分期系统,从而建立了列线图。从诺模图中得到的数据表明,将TRIM 15表达拟合到预后模型中对于预测胃癌患者的OS表现出更好的效率。此外,TRIM 15促进胃癌细胞的迁移、侵袭和上皮-间质转化。结论TRIM 15表达是胃癌患者的一个特异性和独立的不良反应预测因子,该诺模图可能有助于更好的临床治疗。
Abstract Background Gastric cancer is the third leading cause of cancer-related mortality worldwide. Most tripartite motif (TRIM) family proteins are known as E3 ubiquitin ligases and considerable previous research has revealed the involvement of TRIM proteins in carcinogenesis. TRIM15 is a protein from the TRIM family and the aim of this study is to investigate the role of TRIM15 in gastric cancer. Methods We conducted immunohistochemical staining to examine TRIM15 expression using samples from Zhongshan Hospital of Fudan University. We also conducted transwell assay as well as western blot by using gastric cancer cells. Results The expression of TRIM15 in gastric cancer tissues was higher than normal tissues. Present data demonstrated that high TRIM15 staining intensity had a positive relation to tumor invasion depth (P = 0.007), lymph node metastasis (P = 0.013), distant metastasis (P = 0.031), the tumor-node-metastasis (TNM) staging system (P = 0.002) and shorter overall survival (OS) in gastric cancer patients (P < 0.001). It was also worthwhile mentioning that TRIM15 was an adverse prognostic variable for OS. To gain more insight, we incorporated TRIM15 expression into the tumor-node-metastasis (TNM) staging system and thus established a nomogram. Data derived from the nomogram suggested that fitting TRIM15 expression into the prognostic model exhibited better efficiency for predicting OS in gastric cancer patients. Furthermore, TRIM15 promoted migration, invasion and epithelial-mesenchymal transition of gastric cancer cells. Conclusions Together, TRIM15 expression was found as a specific and independent adverse predictor in gastric cancer patients and the nomogram may contribute to better clinical management.
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