Up-regulation of DGAT1 in cancer tissues and tumor-infiltrating macrophages influenced survival of patients with gastric cancer

BMC Cancer. 2021 Mar 9;21(1):252. doi: 10.1186/s12885-021-07976-5.

Abstract

Background: Diacylglycerol-acyltransferase 1 (DGAT1) plays an important role in the energy storage and is involved in cancer progression. A growing number of evidences showed that elevated expression of DGAT1 in cancer tissue indicated a poor outcome in cancer patients. However, the relationship between DGAT1 and gastric cancer is still unclear. Thus, Transcriptomic analysis and in vitro experiments were performed to investigate the role of DGAT1 in gastric cancer, as well as the potential therapy target in gastric cancer treatment.

Methods: We screened the public cancer datasets to identify the expression and function of DGAT1 in gastric cancer and tumor infiltrating lymphocytes. Then we testified the DGAT1 expression and function after sodium oleate treatment in AGS and MKN45 cell line. Finally, we analyzed ration of apoptosis, necrosis in gastric cancer cells by using flow cytometry after administration of DGAT1 inhibitor.

Results: Our results showed a highly expression of DGAT1 in gastric cancer tissues (n = 5, p = 0.0004), and tumor-infiltrating macrophages with elevated DGAT1 expression is associated with poor overall survival in gastric cancer patients. In addition, gastric cell lines AGS (n = 3, p < 0.05) and MKN45 (n = 3, p < 0.01) expressed higher level of DGAT1 than human gastric mucosal epithelial cell line GES-1. Administration of DGAT1 inhibitor effectively suppressed functional factors expression and induced cell death in MKN45.

Conclusion: The findings of this research provide an in-depth insight into the potential role and influences involved in DGAT1 in the gastric cancer patients. And higher expression of DGAT1 leads to lower overall survival (OS) rate in patients with poorly differentiated gastric cancer. Our findings suggest a potential role for DGAT1 in the gastric cancer progression and inhibiting DGAT1 might be a promising strategy in gastric cancer treatment.

Keywords: Cancer treatment; Diacylglycerol-acyltransferase 1; Gastric cancer; Prognosis of patients.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Diacylglycerol O-Acyltransferase / antagonists & inhibitors
  • Diacylglycerol O-Acyltransferase / genetics
  • Diacylglycerol O-Acyltransferase / physiology*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / physiology
  • NADPH Oxidase 2 / physiology
  • Prognosis
  • Stomach Neoplasms / mortality*
  • Stomach Neoplasms / pathology
  • Tumor-Associated Macrophages / physiology*

Substances

  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • CYBB protein, human
  • NADPH Oxidase 2
  • DGAT1 protein, human
  • Diacylglycerol O-Acyltransferase