BACKGROUND

The diphthamide () gene family is a group of genes that encode a set of enzymes that specifically modify eukaryotic elongation factor 2 (eEF2). Although previous studies have shown a link between the genes () and carcinogenesis, it is still unknown how the affect hepatocellular carcinoma (HCC). This study aimed to describe the expression, clinical significance, and potential mechanisms of in HCC.

METHODS

Real-time quantitative polymerase chain reaction (RT-qPCR), Genotype-Tissue Expression (GTEx), and The Cancer Genome Atlas (TCGA) databases were utilized to research the expression of DPHs in HCC. The relationship between the expression of and the clinicopathological characteristics of HCC patients was investigated using TCGA data, and their diagnostic value was evaluated using receiver operating characteristic (ROC) curves and their prognostic value was analyzed using Kaplan-Meier curves and univariate and multivariate Cox regression analyses. Potential reasons for the upregulation of and () expression in HCC were analyzed using multiple databases. Additionally, this study also explored the potential biological functions of in HCC via gene sets enrichment analysis (GSEA). Correlation analysis of expression with immune-related genes and immune checkpoints was performed using Spearman's correlation analysis, and single-sample GSEA was used to assess the distribution of tumor-infiltrating immune cell types.

RESULTS

expression was downregulated in tumor tissues while expression was upregulated and showed a similar expression pattern in HCC. The results of the ROC analysis suggested that had valuable diagnostic properties in HCC. Kaplan-Meier analysis demonstrated that had prognostic predictive value in HCC. Furthermore, univariate and multivariate Cox regression suggested that was an independent predictive factor for HCC. GSEA analysis revealed that might be tightly associated with Pathways in cancer, cell cycles, Fc gamma R mediated phagocytosis, etc. Additionally, expression and numerous immune-related genes showed a positive connection, including chemokines receptor genes, immunosuppressive genes, chemokines genes, human leukocyte antigen (HLA) genes, and immunostimulatory genes. Further analysis of the association between 24 immune infiltrating cells and revealed the greatest negative correlation between natural killer (NK) cells and Th17 cells, but the greatest positive correlation with Th2 cells.

CONCLUSIONS

significantly influence the development and progression of HCC. has significant diagnostic and prognostic potential and may be a promising target for immunotherapy.