Dataset Information

Comprehensive Analysis of Cuproptosis Genes and Identification of Cuproptosis Subtypes in Breast Cancer.

ABSTRACT:

Background

Copper-induced death (cuproptosis) is copper-dependent regulated cell death, which is different from known death mechanisms and is dependent on mitochondrial respiration. However, its effect on breast cancer (BRCA) is unclear.

Objective

The objective of this study is to explore the important clinical significance of cuproptosis genes and to provide a new idea for guiding the personalized immunotherapy strategy of BRCA patients.

Materials and methods

We collected cuproptosis genes from published work. The gene alteration, differential expression, and prognostic value of cuproptosis genes were explored in BRCA based on TCGA database. We identified two subtypes (clusters A and B) by performing unsupervised clustering. The difference between two clusters was deeply explored, including clinical features, differential expressed genes (DEGs), pathways, and immune cell infiltration. Based on the DEGs between two clusters, a cuproptosis score was constructed and its predictive capability for overall survival of BRCA patients was validated.

Results and discussion

Patients with high cuproptosis score have worse survival status, with an increased infiltration level of most immune cells. Further analysis suggested that BRCA patients with high cuproptosis score may be sensitive to immune checkpoint inhibitor (ICI) treatment.

Conclusion

Our findings may improve our understanding of cuproptosis in BRCA and may distinguish patients suitable for ICI treatment.

SUBMITTER: Li J

PROVIDER: S-EPMC10249130 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Comprehensive Analysis of Cuproptosis Genes and Identification of Cuproptosis Subtypes in Breast Cancer.

Li Jialin J Li Lei L Dong Yi Y Zhong Bin B Yin Wei W

Combinatorial chemistry & high throughput screening 20230101 8

<h4>Background</h4>Copper-induced death (cuproptosis) is copper-dependent regulated cell death, which is different from known death mechanisms and is dependent on mitochondrial respiration. However, its effect on breast cancer (BRCA) is unclear.<h4>Objective</h4>The objective of this study is to explore the important clinical significance of cuproptosis genes and to provide a new idea for guiding the personalized immunotherapy strategy of BRCA patients.<h4>Materials and methods</h4>We collected ...[more]

PMID: 36683372

Similar Datasets

Project description:BackgroundCuproptosis is a newly discovered programmed cell death dependent on overload copper-induced mitochondrial respiration dysregulation. The positive response to immunotherapy, one of the most important treatments for invasive breast cancer, depends on the dynamic balance between tumor cells and infiltrating lymphocytes in the tumor microenvironment (TME). However, cuproptosis-related genes (CRGs) in clinical prognosis, immune cell infiltration, and immunotherapy response remain unclear in breast cancer progression.MethodsThe expression and mutation patterns of 12 cuproptosis-related genes were systematically evaluated in the BRCA training group. Through unsupervised clustering analysis and developing a cuproptosis-related scoring system, we further explored the relationship between cuproptosis and breast cancer progression, prognosis, immune cell infiltration, and immunotherapy.ResultsWe identified two distinct CuproptosisClusters, which were correlated with the different patterns between clinicopathological features, prognosis, and immune cell infiltration. Moreover, the differences of the three cuproptosis-related gene subtypes were evaluated based on the CuproptosisCluster-related DEGs. Then, a cuproptosis-related gene signature (PGK1, SLC52A2, SEC14L2, RAD23B, SLC16A6, CCL5, and MAL2) and the scoring system were constructed to quantify the cuproptosis pattern of BRCA patients in the training cohort, and the testing cohorts validated them. Specifically, patients from the low-CRG_score group were characterized by higher immune cell infiltration, immune checkpoint expression, immune checkpoint inhibitor (ICI) scores, and greater sensitivity to immunotherapy. Finally, we screened out RAD23B as a favorable target and indicated its expression was associated with breast cancer progression, drug resistance, and poor prognosis in BRCA patients by performing real-time RT-PCR, cell viability, and IC50 assay.ConclusionsOur results confirmed the essential function of cuproptosis in regulating the progression, prognosis, immune cell infiltration, and response to breast cancer immunotherapy. Quantifying cuproptosis patterns and constructing a CRG_score could help explore the potential molecular mechanisms of cuproptosis regulating BRCA advancement and provide more effective immunotherapy and chemotherapy targets.

Dataset Information

Comprehensive Analysis of Cuproptosis Genes and Identification of Cuproptosis Subtypes in Breast Cancer.

Background

Objective

Materials and methods

Results and discussion

Conclusion

Publications

Comprehensive Analysis of Cuproptosis Genes and Identification of Cuproptosis Subtypes in Breast Cancer.

Similar Datasets

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