Wang_2018_Hum.Pathol_77_35

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 microm 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.