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

Abstract

BackgroundTP53 is one of the most prevalent mutated genes in hepatocellular carcinoma (HCC), while the role of TP53 mutations in HCC metabolic reprogramming remains unclear. MethodsThe 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. ResultsWe 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. ConclusionsThe 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.