Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi, China, 214062; Jiangnan University School of Medicine, Wuxi, China, 214000.
Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi, China, 214062.
Hum Pathol. 2018 Jul;77:35-44. doi: 10.1016/j.humpath.2018.03.013. Epub 2018 Mar 17.
Acyl-CoA thioesterase 1 (ACOT1) 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 μm 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.
酰基辅酶 A 硫酯酶 1(ACOT1)是 ACOT 家族的重要同工酶,可催化脂肪酸酰基辅酶 A 与 CoA-SH 和游离脂肪酸的反应。最近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的异常代谢。然而,ACOT1 在胃癌发展中的功能和贡献仍知之甚少。此外,GLI3 是 Hedgehog 信号通路调节的主要转录因子。GLI3 突变诱导胃癌中腺体扩张和肠上皮化生,表明 GLI3 在癌前过程中发挥作用。因此,我们研究了 ACOT1 表达与胃腺癌中 GLI3 之间的关系。从 280 例胃腺癌中构建组织微阵列。对每个组织微阵列块的 4μm 组织切片进行免疫组织化学方法。我们发现 ACOT1 表达与组织学分级差、T 分期较低、TNM 分期较高和 GLI3 表达增加显著相关。此外,生存分析显示,ACOT1 阳性组的总生存率明显低于 ACOT1 阴性组。此外,在胃腺癌细胞中,GLI3 表达与 ACOT1 表达呈显著正相关。综上所述,这些发现表明,ACOT1 的高表达通过增加潜在的肿瘤促进蛋白 GLI3,与胃腺癌中的关键临床病理参数和不良预后相关。