ACOT1 expression is associated with poor prognosis in gastric adenocarcinoma
ACOT1 expression is associated with poor prognosis in gastric adenocarcinoma
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ACOT1表达与胃腺癌不良预后相关
DOI：
10.1016/j.humpath.2018.03.013
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发表时间：
2018-07-01
期刊：
影响因子：
3.3
通讯作者：
Mao, Yong
中科院分区：
文献类型：
--
作者：
Wang, Fang;Wu, Jingyi;Mao, Yong
酰基辅酶A硫酯酶1（ACOTI）是ACOT家族的重要同种型，其催化脂肪酰基辅酶A反应为辅酶A-SH和游离脂肪酸。近年来对胃肠道肿瘤代谢的研究表明，肿瘤进展过程中存在脂质和脂肪酸代谢异常。然而，ACOT 1在胃癌发生发展中的功能和贡献仍然知之甚少。此外，GLI 3是调节hedgehog信号传导的主要转录因子。GLI 3突变诱导胃癌中的腺体扩张和肠上皮化生，这表明GLI 3在癌前过程中的作用。因此，我们研究了胃腺癌中ACOT 1表达和GLI 3之间的关系。构建了280例胃腺癌组织芯片。对来自每个组织微阵列块的4 μ m的组织切片进行免疫组织化学方法。我们发现ACOT 1表达与组织学分级差、T分级低、TNM分期和GLI 3表达增加显著相关。此外，生存分析显示，与ACOT 1阴性组相比，ACOT 1阳性组的总生存率显著降低。GLI 3与ACOT 1在胃腺癌细胞中的表达呈显著正相关。总之，这些研究结果表明，ACOT 1的表达增加与胃腺癌的关键临床病理参数和不良预后相关，通过增加潜在的肿瘤促进蛋白GLI 3的表达。(C)2018由Elsevier Inc.出版
Acyl-CoA thioesterase 1 (ACOTI) is an important isoform of the ACOT family that catalyzes the reaction of fatty acyl-CoAs to CoA-SH and free fatty acids. Recent studies of gastrointestinal tumor metabolism suggest that there is abnormal metabolism of lipids and fatty acids during tumor progression. However, the function and contribution of ACOT1 in gastric cancer development are still poorly understood. In addition, GLI3 is a major transcription factor in the regulation of hedgehog signaling. GLI3 mutations induce glandular expansion and intestinal metaplasia in gastric cancer, which indicates a role for GLI3 in the preneoplastic process. Thus, we investigated the relationship between ACOT1 expression and GLI3 in gastric adenocarcinoma. A tissue microarray was constructed from 280 cases of gastric adenocarcinoma. The immunohistochemistry method was performed on tissue sections of 4 mu m from each tissue microarray block. We found a significant correlation between ACOT1 expression and poor histologic grade, a lower T category, TNM stage, and increased GLI3 expression. In addition, the survival analysis revealed that the ACOT1-positive group had significantly decreased overall survival rates compared with the ACOT1-negative group. Furthermore, GLI3 expression had a significant positive correlation with ACOT1 expression in gastric adenocarcinoma cells. In summary, these findings demonstrate that increased expression of ACOT1 is correlated with pivotal clinicopathological parameters and poor prognosis in gastric adenocarcinoma through increased expression of the potential tumor-promoting protein GLI3. (C) 2018 Published by Elsevier Inc.