Clinical importance of FASN in relation to HIF-1α and SREBP-1c in gastric adenocarcinoma

Aims: Identifying alterations in lipid metabolism along gastric adenocarcinoma (GA) tumorigenesis pathways could lead to a new approach for potential diagnosis, efficient prediction and promising therapeutic strategies. This study aimed to identify the possible effect of HIF-1 alpha on FASN and SREBP-1c regulation in GA. Main methods: AGS cell line was cultured in normoxic and hypoxic conditions, and HIF-1 alpha, FASN and SREBP-1c gene expression were analyzed by qRT-PCR and Western blot. Serum HIF-1 alpha, FASN and insulin concentration were measured in 112 GA patients and 156 control cases by ELISA, and immunohistochemical method was employed to analyze SREBP-1c expression. Tissue mRNA expression of SREBP-1c, FASN and HIF-1 alpha were determined by qRT-PCR. Key findings: In vitro findings indicate upregulation of HIF-1 alpha, FASN and SREBP-1c gene and protein expression in the hypoxic culture of AGS cells. High circulating levels of HIF-1 alpha and FASN were significantly observed in GA patients compared to the controls. HIF-1 alpha, SREBP-1c and FASN gene expression were higher in GA vs. controls. In addition, SREBP-1c protein level was enhanced in GA tissues compared to controls. Furthermore, elevated serum levels of HIF-1a and FASN and expression of HIF-1 alpha, SREBP-1c and FASN genes were associated with unfavorable clinicopathological features such as diffuse type tumor and poor survival. Significance: The results by correlating increased levels of FASN to those of HIF-1 alpha and SREBP-1c are consistent with a possible up-regulation of FASN upon induction of HIF-1 alpha through SREBP-1c.