Alcohol dehydrogenase 4 is a TP53‑associated gene signature for the prediction of prognosis in hepatocellular carcinoma

作者：Yuan Zhang, Huihong Jiang, Zhenyu Wang, Bo Zhai, Moubin Lin · 发表于：Oncology Letters · 年份：2022 · DOI：10.3892/ol.2022.13589 · 被引用次数：23 · 研究领域：Cancer, Hypoxia, and Metabolism、Ferroptosis and cancer prognosis、Liver Disease Diagnosis and Treatment

Tumor protein p53 (TP53) is one of the most frequently mutated genes in hepatocellular carcinoma (HCC), an event that has been associated with a poor prognosis. Therefore, availability of an accurate prognostic signature would be beneficial for improving therapeutic efficacy and patient prognosis. In the present study, HCC genetic mutation data, transcriptomic data and clinical data were downloaded from The Cancer Genome Atlas database to screen for specific TP53-associated signatures based on differentially expressed genes. Subsequently, the predictive value of any signatures found for the overall survival (OS) and the immune response were investigated, followed by validation in clinical specimens. The present study revealed 270 mutant genes, of which 28% were TP53 mutations. In addition, 81 upregulated genes and 27 downregulated genes were identified. Enrichment analysis revealed that mutant TP53 was particularly enriched for pathways associated with the cell cycle and cell metabolism, and whilst clustered, most enriched for terms associated with metabolic processes and the immune response. The alcohol dehydrogenase 4 (ADH4) gene was selected using univariate and multivariate Cox regression analysis. A nomogram was constructed to validate this prognostic signature. Patients in the low-ADH4 expression group displayed significantly worse OS time regardless of the TP53 mutation status compared with the high-ADH4 expression group. In addition, a higher degree of B-cell infiltra...