A TP53-associated metabolic gene signature for the prediction of overall survival and therapeutic responses in hepatocellular carcinoma

Background: TP53 is one of the most prevalent mutated genes in hepatocellular carcinoma (HCC), while the role of TP53 mutations in HCC metabolic reprogramming remains unclear.Methods: The differential analysis of gene expression profile between HCC patients with wild-type and mutated TP53 was performed to identify TP53-associated metabolic genes (TMGs). The TMGs were utilized to construct and validate a TP53-associated metabolic gene signature (TMS). Comprehensive bioinformatics analyses were performed to explore clinical application value and biological interpretability of TMS.Results: We identified 86 TMGs based on the TP53 mutation status. TMS including CYP26B1, CYP2C9, G6PD, PYGM and TKTL1 was constructed and validated to identify the low-TMSscore group had a better prognosis than the high-TMSscore group. Tryptophan metabolism and fatty acid metabolism were significantly enriched in the low-TMSscore group. Moreover, it was characterized by a higher abundance of gamma delta T cell and natural killer cell than the high-TMSscore group. Compared to the high-TMSscore group, the low-TMSscore group was more likely to respond to immune checkpoint therapy.Conclusions: The TMS is a potential strategy for prognostic prediction and immune checkpoint therapy guidance for HCC patients. Our study provides new insights into the involvement of TP53 mutations in tumor metabolic reprogramming.