Role of ACLY in the development of gastric cancer under hyperglycemic conditions

Abstract

To investigate the impact of hyperglycemia on the prognosis of patients with gastric cancer and identify key molecules associated with high glucose levels in gastric cancer development, RNA sequencing data and clinical features of gastric cancer patients were obtained from The Cancer Genome Atlas (TCGA) database. High glucose‐related genes strongly associated with gastric cancer were identified using weighted gene co‐expression network and differential analyses. A gastric cancer prognosis signature was constructed based on these genes and patients were categorized into high‐ and low‐risk groups. The immune statuses of the two patient groups were compared. ATP citrate lyase (ACLY), a gene significantly related to the prognosis, was found to be upregulated upon high‐glucose stimulation. Immunohistochemistry and molecular analyses confirmed high ACLY expression in gastric cancer tissues and cells. Gene Set Enrichment Analysis (GSEA) revealed the involvement of ACLY in cell cycle and DNA replication processes. Inhibition of ACLY affected the proliferation and migration of gastric cancer cells induced by high glucose levels. These findings suggest that ACLY, as a high glucose‐related gene, plays a critical role in gastric cancer progression.