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Prognostic implication and immunotherapy response prediction of a ubiquitination-related gene signature in breast cancer

Breast cancer (BC) is one of the most common tumor types and has poor outcomes. In this study, a ubiquitination-related prognostic signature was constructed, and its association with immunotherapy response in BC was explored. A list of ubiquitination-related genes was obtained from the molecular signatures database, and a ubiquitination-related gene signature was obtained by least absolute shrinkage and selection operator Cox regression. The genes, TCN1, DIRAS3, and IZUMO4, had significant influence on BC outcomes. Patients were categorized into two clusters-a high-risk group with poor survival and a low-risk group with greater chances of controlling BC progression. Univariate and multivariate Cox regression analyses revealed that the risk signature was an independent prognostic factor for BC. Gene set enrichment analysis suggested that the high-risk group was enriched in cell cycle and DNA replication pathways. The risk score was positively linked to the tumor microenvironment and negatively correlated with the immunotherapy response. The IC50 values for rapamycin were higher in the low-risk group, whereas those for axitinib, AZD6244, erlotinib, GDC0941, GSK650394, GSK269962A, lapatinib, and PD0325901 were higher in the high-risk group. Therefore, the ubiquitination-related signature is considered a promising tool for predicting a BC patient's immunotherapy response.

 

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The study you mentioned focuses on the construction of a prognostic signature based on ubiquitination-related genes and its association with immunotherapy response in breast cancer (BC). Here are the key findings of the study:

Gene Selection: The researchers obtained a list of ubiquitination-related genes from the molecular signatures database and used a statistical technique called least absolute shrinkage and selection operator (LASSO) Cox regression to identify a subset of genes that were most predictive of BC outcomes. From this analysis, three genes, TCN1, DIRAS3, and IZUMO4, were found to have a significant influence on BC outcomes.

Risk Stratification: Using the identified gene signature, the researchers categorized BC patients into two clusters: a high-risk group with poor survival and a low-risk group with a higher chance of controlling BC progression. This risk stratification based on the gene signature could help identify patients with different prognoses.

Prognostic Value: Univariate and multivariate Cox regression analyses were performed, and the results showed that the ubiquitination-related gene signature was an independent prognostic factor for BC. This means that the gene signature had predictive power in determining the outcomes of BC patients, regardless of other clinical factors.

Pathway Analysis: Gene set enrichment analysis revealed that the high-risk group, associated with poor survival, was enriched in pathways related to cell cycle and DNA replication. This suggests that dysregulation of these processes may contribute to the aggressiveness of BC in this group.

Tumor Microenvironment and Immunotherapy Response: The researchers found a positive association between the risk score derived from the gene signature and the tumor microenvironment, indicating that high-risk BC patients may have a more immunosuppressive microenvironment.

Additionally, the risk score was negatively correlated with the response to immunotherapy. This suggests that patients with a high-risk signature may have a reduced likelihood of responding favorably to immunotherapy treatments.

Drug Sensitivity: The study also investigated the association between the gene signature and the response to specific drugs. The IC50 values (a measure of drug sensitivity) for rapamycin were higher in the low-risk group, while IC50 values for axitinib, AZD6244, erlotinib, GDC0941, GSK650394, GSK269962A, lapatinib, and PD0325901 were higher in the high-risk group. This indicates that the drug sensitivity profiles may differ between the risk groups, suggesting potential differences in treatment response.

In summary, the ubiquitination-related gene signature identified in this study shows promise as a prognostic tool for predicting BC patient outcomes and may also provide insights into the immunotherapy response and drug sensitivity patterns in BC.

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