Abstract
BACKGROUND: Gastric cancer (GC) is a leading cause of cancer-related mortality worldwide, and lipid metabolism reprogramming plays a crucial role in tumor progression. ATP citrate lyase (ACLY), a key enzyme in de novo lipid synthesis, has been implicated in multiple cancers, but its role in GC remains incompletely understood. This study aimed to investigate the expression, prognostic significance, and potential molecular mechanisms of ACLY in GC, with a particular focus on its relationship with lipid metabolism and ubiquitination. METHODS: VOSviewer and Bibliometrix were used for analysis of the PubMed database related to GC and lipid metabolism. The expression levels of ACLY in GC tissues and normal tissues in The Cancer Genome Atlas (TCGA) database were compared and western blot was used to detect. The relationship between ACLY and the prognosis of GC patients was analyzed through bioinformatics. Genome Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment were performed for ACLY-related genes, and three gene data related to ACLY, lipid metabolism and GC were analyzed. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyzed substances in 2-furoic acid-treated and normal HGC-27 cells. RESULTS: Lipid metabolism and patient prognosis is a hot topic in the field of GC. Compared with that in normal tissues, the level of ACLY in GC tissues is significantly greater, and it is associated with poor patient prognosis. The prognosis of patients with GC is related to age, node (N) stage and metastasis (M) stage. The functions of the ACLY-related genes in cell differentiation and the structure, signal transduction and enzyme activity of GC are enriched. ACLY is correlated with lipid metabolism genes in GC. The content of fatty acids in GC cells decreased after 2-furoic acid treatment. CONCLUSIONS: ACLY regulates lipid metabolism to affect the occurrence and development of GC.