Pan-cancer Analysis of TP53 Expression: Prognostic Significance and Identification of Diagnostic and Prognostic Biomarkers in Hepatocellular Carcinoma

Abstract Background: Hepatocellular carcinoma (LIHC) is a common and aggressive liver malignancy, often diagnosed at advanced stages. Dysregulation of the TP53 tumor suppressor gene critical for cell cycle control, apoptosis, and genomic stabilityis frequently observed in LIHC; however, its prognostic value remains uncertain. Objectives: To investigate TP53 expression levels, prognostic relevance, and molecular interactions in LIHC within a broader pan-cancer context. Methods: Publicly available datasets from TCGA and GEO were analyzed. TP53 differential expression was evaluated using TIMER 2.0, GEPIA, and UALCAN. Survival analysis was performed via Kaplan-Meier Plotter, GEPIA, and UALCAN. Genomic alterations were assessed through cBioPortal. Gene expression validation was conducted using GEO2R and ggplot2. Protein-protein interaction networks were constructed using STRING and GeneMANIA. Results: TP53 mRNA expression was significantly elevated in LIHC tumor tissues compared to normal liver tissues (p < 0.05). Promoter hypo-methylation was noted in tumor samples, potentially contributing to this up-regulation. Survival analysis revealed conflicting findings: Kaplan-Meier Plotter associated high TP53 expression with better prognosis (HR = 0.65, p = 0.029), whereas GEPIA and UALCAN linked high expression with poorer outcomes. Furthermore, TP53 expression positively correlated with immune cell infiltration and advanced clinical stage, suggesting a complex role in tumor progression. Conclusion: TP53 demonstrates a dual, context-dependent role in LIHC, acting as both a tumor suppressor and potential oncogenic driver. Its variable expression patterns and inconsistent prognostic associations highlight its potential as a diagnostic and prognostic biomarker and support the need for further functional and clinical validation.