ADH4 Is A TP53-Associated Immune-Metabolic Signature For The Prediction Of Prognosis In Hepatocellular Carcinoma

Abstract Background: Tumor protein p53 (TP53) is one of the most frequent mutated genes in hepatocellular carcinoma (HCC), whose mutations influenced tumor microenvironment (TME) and are associated with a worse prognosis. Thus, finding out an accurate prognostic signature could be beneficial for improving the prognosis of HCC.Methods: HCC genetic mutation data, transcriptome data, and clinical data were downloaded from the TCGA database to clarify specific TP53-associated signatures based on differential expression genes (DEGs). We investigated the predictive value of this signature on the overall survival (OS), immune analysis, and validation in clinical specimens.Results: In total, our research exhibited 270 mutant genes, and TP53 mutation occupied 28%. Besides, 81 upregulated genes and 27 downregulated genes were identified. Enrichment analysis showed that mutant-type TP53 were enriched for pathways related to cell cycle and cell metabolism, while clustered most enriched for terms related to metabolic process and immune response. The gene alcohol dehydrogenase4 (ADH4) was identified by univariate and multivariate Cox regression analysis and a nomogram was also established to validate this prognostic signature. Moreover, the low-ADH4 group in both TP53 mutant type and wild type displayed significantly worse OS than the high-ADH4 group. In addition, immune infiltration with higher expression of B cell groups showed a differential immune microenvironment. Especially, ADH4 expression and the prognostic prediction values were further validated in clinical samples.Conclusions: The TP53-associated immune-metabolic signature is a specific and independent prognostic biomarker for HCC patients, and could provide a potential prognostic biomarker for the development of novel immunotherapies.