The combined expressions of B7H4 and ACOT4 in cancer-associated fibroblasts are related to poor prognosis in patients with gastric carcinoma.

ABSTRACT

B7H4 is a member of the B7 family, which is expressed on antigen-presenting cells (APCs) and which negatively regulates the immune response of T cells through the inhibition of their proliferation, cytokine production, and cell cycle progression. Acyl-CoA thioesterase 4 (ACOT4) is an isoform of the ACOTs family that catalyzes the hydrolysis of fatty acyl-CoA to CoA-SH and free fatty acids. An abnormal metabolism of lipids and fatty acids is observed during tumor progression. In our study, a tissue microarray was constructed from 288 cases of gastric adenocarcinoma (GC). ACOT4 expression in cancer-associated fibroblasts (CAFs) and B7H4 expression in cancer tissues were analyzed by immunohistochemistry. The correlations among B7H4 in GC cells, ACOT4 in CAFs, and survival were analyzed. The results showed that the expression rate of B7H4 in tumor cells and ACOT4 in CAFs in 288 tissues was 71.9% (207/288) and 26.4% (76/288), respectively, and a Kaplan-Meier survival analysis showed that a low expression of ACOT4 in fibroblasts was positively correlated with poor survival. However, in a subgroup showing a high ACOT4 expression, the overall survival rate was associated with a high expression of B7H4 and correlated with poor prognosis in GC. In conclusion, ACOT4 expression in CAFs could be an independent prognostic factor for GC patients, and the co-expression with B7H4 in cancer tissues was significantly correlated with GC patients' prognosis. This evidence can represent a comprehensive prediction and a targeted therapy for gastric cancer patients. Tumor immunotherapy targeting might be affected by tumor microenvironment metabolism.