Prognostic and Immune Landscape Analysis of Ubiquitination-related Genes in Hepatocellular Carcinoma: Based on Bulk and Single-cell RNA Sequencing Data.
J Cancer
; 15(9): 2580-2600, 2024.
Article
em En
| MEDLINE
| ID: mdl-38577593
ABSTRACT
Background:
Despite significant advances in tumor immunotherapy, hepatocellular carcinoma (HCC) remains a malignancy with a challenging prognosis. The increasing research emphasizes the crucial role of ubiquitination in tumor immunotherapy. However, the establishment of prognostic signatures based on ubiquitination-related genes (UbRGs) and their role in immunotherapy are still lacking in HCC.Methods:
We employed datasets from TCGA and GEO for transcriptome differential expression analysis and single-cell RNA sequencing analysis. Applying weighted gene co-expression network analysis, cox regression, lasso, selection and visualization of the most relevant features, and gradient boosting machine, we identified hub UbRGs as a gene signature to develop a prognostic model. We evaluated the predictive utility concerning clinical characteristics as well as its role in the immune landscape and immunotherapy potential. Additionally, western blotting, reverse transcription-quantitative PCR, and immunofluorescence were employed to detect the expression and sub-localization of hub genes.Results:
Three hub UbRGs (BOP1, CDC20, and UBE2S) were identified as a gene signature. In particular, the high-risk group exhibited notable characteristics, including higher tumor mutation burden, enrichment in immune-related pathways, up-regulation immune checkpoint, and higher immunity scores. Treatment response to immunotherapy varied based on the expression of PD-1 and CTLA-4. Furthermore, single-cell data analysis revealed heterogeneous expression of hub UbRGs across different cell subtypes, while cytological experiments provided additional confirmation of the high expression of hub UbRGs in HCC.Conclusion:
Our study provides valuable insights into the identification of novel ubiquitination-related biomarkers with potential applications for prognosis, immunotherapy prediction, and drug sensitivity in HCC.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
J Cancer
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China