Recent studies suggest that cuproptosis, a novel mode of cell death, may be associated with the development of cancer. However, no studies are showing its role in tumorigenesis, progression, and prognosis. In the present study, we comprehensively analyzed the expression difference, gene variation and methylation modification of cuproptosis-related genes (CRGs) in pan-cancer. Then, Single sample gene set enrichment analysis (ssGSEA) was used to calculate individual cuproptosis scores (CS). The association of CS with copy number variation, clinical features, immune-related genes, TMB, MSI, and tumor immune dysfunction and exclusion (TIDE) was comprehensively assessed. Single-cell transcriptome sequencing (scRNA-seq) to analyze the activation of cuproptosis in the tumor microenvironment. Immunohistochemistry (IHC) were used to validate the expression of cuproptosis hub-gene. Our study shows that CRGs were significantly expressed in a variety of tumors, and CDKN2A had the highest mutation frequency (49%) in all tumors. A significant increase in the CS was observed in most cancers and were associated with poor prognosis in the majority of tumors. CS was significantly negatively correlated with tumor microenvironment scores in more than 10 tumors and positively correlated with PD-L1 in 11 tumors, suggesting involvement in tumor immune escape. scRNA-seq suggests that CRG scores significantly increased in the cancer cells. This study opens avenues for further research on the role of cuproptosis in the occurrence and development of cancer and the development of targeted therapies based on cuproptosis.
Background: Monkeypox is a zoonotic disease caused by monkeypox virus, and most infections cause systemic disease. Tumor patients are susceptible to various viruses, but there are few reports on the effects of genes related to monkeypox virus infection on the tumor microenvironment. Therefore, we need to further explore the expression of genes associated with monkeypox infection in tumor patients and the potential immune mechanisms in order to improve the survival and prognosis of tumor patients. Methods: The gene expression, genetic variation, mRNA sequencing samples, clinical and methylation datas were from 33 cancer types of TCGG database. Single-cell transcriptome sequencing (scRNA-seq) was used to analyze the activation of monkeypox related genes in the tumor microenvironment. Then, Single sample gene set enrichment analysis (ssGSEA) and immunohistochemistry (IHC) were used in our research. The relationship between monkeypox and gene expression, clinical features, immune microenvironment, TMB and MSI was comprehensively evaluated. Results: In this study, monkeypox-related genes were found to be closely associated with most tumorigenesis as well as drug sensitivity. Additionally, cellular enrichment pathways suggest that monkeypox is closely associated with invasion, cell cycle, DNA damage and repair. The prognostic value on monkeypox-related genes was evaluated, and it was found that monkeypox is a risk factor. Moreover,monkeypox-related genes are positively associated with immune cells as well as immune checkpoints in most tumors. Analysis of scRNA-seq indicates that monkeypox differs significantly among cells of the tumor microenvironment. Conclusion: The current study explored the monkeypox-related genes in pan-cancer for the first time and provides new insights. We found that monkeypox-related genes are closely associated with the formation of immune microenvironments and immunotherapeutic efficacy of most tumor, which provides new ideas for the prevention and treatment of monkeypox and tumors.
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