Copper and cuproptosis-related genes in hepatocellular carcinoma: therapeutic biomarkers targeting tumor immune microenvironment and immune checkpoints.
Front Immunol
; 14: 1123231, 2023.
Article
em En
| MEDLINE
| ID: mdl-37153542
ABSTRACT
Background:
Hepatocellular carcinoma (HCC), one of the most common cancers worldwide, exhibits high immune heterogeneity and mortality. Emerging studies suggest that copper (Cu) plays a key role in cell survival. However, the relationship between Cu and tumor development remains unclear.Methods:
We investigated the effects of Cu and cuproptosis-related genes (CRGs) in patients with HCC in the TCGA-LIHC (The Cancer Genome Atlas-Liver cancer, n = 347) and ICGC-LIRI-JP (International Cancer Genome Consortium-Liver Cancer-Riken-Japan, n = 203) datasets. Prognostic genes were identified by survival analysis, and a least absolute shrinkage and selection operator (Lasso) regression model was constructed using the prognostic genes in the two datasets. Additionally, we analyzed differentially expressed genes and signal pathway enrichment. We also evaluated the effects of CRGs on tumor immune cell infiltration and their co-expression with immune checkpoint genes (ICGs) and performed validation in different tumor immune microenvironments (TIMs). Finally, we performed validation using clinical samples and predicted the prognosis of patients with HCC using a nomogram.Results:
A total of 59 CRGs were included for analysis, and 15 genes that significantly influenced the survival of patients in the two datasets were identified. Patients were grouped by risk scores, and pathway enrichment analysis suggested that immune-related pathways were substantially enriched in both datasets. Tumor immune cell infiltration analysis and clinical validation revealed that PRNP (Prion protein), SNCA (Synuclein alpha), and COX17 (Cytochrome c oxidase copper chaperone COX17) may be closely correlated with immune cell infiltration and ICG expression. A nomogram was constructed to predict the prognosis of patients with HCC using patients' characteristics and risk scores.Conclusion:
CRGs may regulate the development of HCC by targeting the TIM and ICGs. CRGs such as PRNP, SNCA, and COX17 could be promising targets for HCC immune therapy in the future.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apoptose
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Carcinoma Hepatocelular
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Neoplasias Hepáticas
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Front Immunol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
CH
/
SUIZA
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SUÍÇA
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SWITZERLAND