An abnormally high expression of ISL-1 represents a potential prognostic factor in gastric cancer

An abnormally high expression of ISL-1 represents a potential prognostic factor in gastric cancer
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ISL-1 的异常高表达代表胃癌的潜在预后因素。

DOI:
10.1016/j.humpath.2015.05.006
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发表时间:
2015-09-01
期刊:
影响因子:
3.3
通讯作者:
Zhou, Chunyan
Zhou, Chunyan
中科院分区:
医学3区
文献类型:
--
作者:
Guo, Chen;Wang, Weiping;Zhou, Chunyan

文献摘要

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胰岛素基因增强子结合蛋白-1(ISL-1)是一种参与心脏、运动神经元和胰腺发育的转录因子。我们以前的研究表明ISL-1在胃癌中过表达,而在其他胃肠道肿瘤中不表达。然而,没有ISL-1在胃癌中的免疫组化或临床病理学研究已经进行。本研究旨在探讨ISL-1在胃癌组织中的表达及其预后价值。建立裸鼠移植瘤模型,研究ISL-1在体内肿瘤发生发展中的作用。ISL-1过表达可显著增强NIH 3 T3细胞的体内致瘤性。应用免疫组织化学方法检测456例胃癌组织及正常胃黏膜组织中ISL-1的表达。ISL-1在胃腺癌组织中的表达明显高于正常胃组织。ISL-1表达与浸润深度、淋巴结转移、TNM分期和组织学分级显著相关(P <0.05,卡方检验)。ISL-1阳性表达与胃癌5年总生存率相关(P = 0.001,对数秩检验)。多因素考克斯回归分析显示ISL-1表达(P = 0.047)可能是影响胃癌总生存率的独立预后因素。这项研究表明,ISL-1可能是一个有用的预后生物标志物,并可能成为胃腺癌的一个新的治疗靶点。(C)2015 Elsevier Inc. All rights reserved.
Insulin gene enhancer binding protein-1 (ISL-1) is a transcription factor involved in development of the heart, motor neurons, and pancreas. Our previous study indicated that ISL-1 was overexpressed in gastric cancer but not in other gastrointestinal tumors. However, no immunohistochemical or clinicopathological studies of ISL-1 in gastric carcinoma have been performed. The aim of this study was to determine the expression and prognostic value of ISL-1 in gastric carcinoma. A nude mouse xenograft model was established to study the role of ISL-1 on cancer genesis and development in vivo. Overexpression of ISL-1 significantly enhanced the tumorigenicity of NIH3T3 cells in vivo. ISL-1 expression was evaluated using immunohistochemistry in 456 human gastric carcinoma and normal tissues. ISL-1 was significantly overexpressed in gastric adenocarcinoma compared with normal gastric tissues. ISL-1 expression was significantly associated with depth of invasion, lymph node metastasis, TNM stage, and histological grade (P < .05, chi(2) test). Positive ISL-1 expression was associated with poorer 5-year overall survival in gastric cancer (P = .001, log-rank test). Multivariate Cox regression analysis demonstrated that ISL-1 expression (P = .047) could be an independent prognostic factor for overall survival in gastric carcinoma. This study suggests that ISL-1 may be a useful prognostic biomarker and may represent a novel therapeutic target for gastric adenocarcinoma. (C) 2015 Elsevier Inc. All rights reserved.