Open Access

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

  • Authors:
    • Yuan Zhang
    • Hui-Hong Jiang
    • Zhen-Yu Wang
    • Bo Zhai
    • Mou-Bin Lin
  • View Affiliations

  • Published online on: November 8, 2022     https://doi.org/10.3892/ol.2022.13589
  • Article Number: 3
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

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 infiltration was observed in the low‑ADH4 expression group, revealing differential immune microenvironments. Subsequently, ADH4 expression and the prognostic prediction values were validated further in clinical HCC samples by IHC assay, Risk score, OS analysis and ROC analysis. To conclude, these data suggest that the TP53‑associated immune‑metabolic signature is a specific and independent prognostic biomarker for patients with HCC that will help to facilitate novel immunotherapy development.
View Figures
View References

Related Articles

Journal Cover

January-2023
Volume 25 Issue 1

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Zhang Y, Jiang H, Wang Z, Zhai B and Lin M: Alcohol dehydrogenase 4 is a TP53‑associated gene signature for the prediction of prognosis in hepatocellular carcinoma. Oncol Lett 25: 3, 2023
APA
Zhang, Y., Jiang, H., Wang, Z., Zhai, B., & Lin, M. (2023). Alcohol dehydrogenase 4 is a TP53‑associated gene signature for the prediction of prognosis in hepatocellular carcinoma. Oncology Letters, 25, 3. https://doi.org/10.3892/ol.2022.13589
MLA
Zhang, Y., Jiang, H., Wang, Z., Zhai, B., Lin, M."Alcohol dehydrogenase 4 is a TP53‑associated gene signature for the prediction of prognosis in hepatocellular carcinoma". Oncology Letters 25.1 (2023): 3.
Chicago
Zhang, Y., Jiang, H., Wang, Z., Zhai, B., Lin, M."Alcohol dehydrogenase 4 is a TP53‑associated gene signature for the prediction of prognosis in hepatocellular carcinoma". Oncology Letters 25, no. 1 (2023): 3. https://doi.org/10.3892/ol.2022.13589