Abstract
Ferroptosis results from metabolic dysregulation and is closely linked to liver cancer. Although a ferroptosis-related gene signature in liver cancer has been established, the precise regulatory mechanism is still unclear. To identify shared pathogenic genes linked to ferroptosis across liver cancer patients from diverse racial backgrounds, we evaluated various ferroptosis-related genes, constructing a signature for both Asian and White patients using The Cancer Genome Atlas (TCGA) database. Based on the differential expression and functionality of ferroptosis-associated genes, we selected Farnesyl diphosphate farnesyl transferase 1 (FDFT1), Acyl-CoA synthetase long-chain 4 (ACSL4) and Endoplasmic reticulum membrane protein complex 2 (EMC2) for further study in liver cancer cells. FDFT1, ACSL4 and EMC2 induced ferroptosis of liver cancer cells though upregulation of reactive oxygen species (ROS) levels and downregulation of glutathione peroxidase (GPX4). Current data indicate no notable influence of racial differences on the functionality of ferroptosis-related genes. Our data suggests potential novel therapeutic avenues for liver cancer treatment.