TFPT Abundance Is Associated with Growth-Related Phenotypes and Cellular Features Linked to Lipid Peroxidation Defense in Hepatocellular Carcinoma

TCF3 fusion partner (TFPT) remains insufficiently characterized in hepatocellular carcinoma (HCC), particularly in relation to tumor growth and cellular features linked to lipid peroxidation defense. We integrated public transcriptomic and clinical datasets and established stable TFPT-knockdown and TFPT-overexpression models in MHCC97-H and Huh-7 cells. TFPT expression was higher in HCC tissues and selected HCC cell lines. In TCGA-LIHC, higher TFPT expression was associated with shorter overall survival after multivariable adjustment (HR, 1.37; 95% CI, 1.06–1.77), although this association was not reproduced in GSE14520. TFPT-high tumors were enriched for E2F Targets, MYC Targets, G2/M Checkpoint, and metabolic and cellular-stress-related programs. Internally constructed descriptive scores related to lipid peroxidation defense were higher in TFPT-high tumors but showed limited external reproducibility. In vitro, shTFPT cells showed lower CCK-8 signals, colony formation, monolayer closure, GSH levels, total glutathione peroxidase activity, and relative GPX4, SLC7A11, and FSP1 protein abundance, together with higher Fe2+ and MDA levels and higher BODIPY-C11 green-to-red fluorescence ratios; oeTFPT cells showed opposite patterns. These findings support an association between TFPT abundance and growth-related phenotypes and cellular features linked to lipid peroxidation defense in HCC, without establishing direct molecular regulation, ferroptotic cell death, causality, or independently validated prognostic utility.