TP53, HIF1A, and CDKN2A in Hepatocellular Carcinoma: Roles in Senescence, Ferroptosis, and Prognosis.

[INTRODUCTION] The aim of this study was to evaluate the association between genes related to cellular senescence and ferroptosis and their relevance to hepatocellular carcinoma (HCC).

[METHODS] Genes associated with senescence and ferroptosis in HCC were retrieved from public databases. A protein-protein interaction network was constructed to identify for hub genes and validate their expression. Diagnostic performance was evaluated using receiver operating characteristic curve analysis, while prognostic significance was determined through Kaplan-Meier analysis. A prognostic nomogram model was developed based on selected hub genes and tumor node metastasis staging.

[RESULTS] A total of 52 senescence-ferroptosis-related genes were identified in HCC. Receiver operating characteristic analysis indicated moderate to high diagnostic efficacy for TP53 (area under the curve [AUC] = 0.723, CI: 0.669-0.776), JUN (AUC = 0.733, CI: 0.659-0.806), RELA (AUC = 0.854, CI: 0.808-0.901), and CDKN2A (AUC = 0.953, CI: 0.932-0.974). Kaplan-Meier analysis revealed that TP53 , HIF1A , and CDKN2A were significantly associated with overall survival in patients with HCC. A nomogram model incorporating these 3 genes and tumor node metastasis staging achieved a concordance index (C-index) of 0.699. Calibration curves indicated concordance between the predicted and observed survival probabilities at 1-, 2-, and 3-year intervals.

[DISCUSSION] The senescence-ferroptosis-related genes TP53, HIF1A, and CDKN2A demonstrated potential as diagnostic and prognostic biomarkers in HCC. The developed nomogram may support individualized prognostic assessment and inform early diagnostic and therapeutic strategies in patients with HCC.