Abstract
BackgroundDiacylglycerol-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.MethodsWe 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.ResultsOur 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.ConclusionThe 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.
Highlights
Diacylglycerol-acyltransferase 1 (DGAT1) plays an important role in the energy storage and is involved in cancer progression
DGAT1 was highly expressed in patients with gastric cancer
Kaplan– Meier curves showed that aberrant expression of DGAT1 in immune cells and tumor tissues predict a poor prognosis in gastric cancer patients, and administration of iDGAT1 effectively inhibited reactive oxygen species expression in gastric cancer cell line, suggesting the considerable interest in DGAT1 as a potential target for the diagnosis and treatment of gastric cancer, which indicated a potential clinical impact for controlling gastric cancer
Summary
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. Gastric cancer is responsible for more than 900,000 deaths in the past year, rapidly growing number of new cases and deaths make it the third leading cause of cancer death in the world [1, 2]. Data from The World Health Organization (WHO) demonstrated that a growing number of new cases of gastric cancer occur in developing countries [3]. Clinical data showed that advanced stage of gastric patients have poor five-year survival rate [5]. Evidence suggests that early diagnosis is critical for gastric cancer treatment and improving sufferers’ survival [6]. Despite its extensive clinical studies, early diagnosis of gastric cancer still cannot meet the requirement due to the lack of appropriate biomarkers [6]
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