Comprehensive analysis of cuproptosis-related genes and tumor microenvironment infiltration characterization in breast cancer
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Published on: July 29, 2011
Shaoran Song1,2, Miao Zhang1,2, Peiling Xie3
1Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Insights
Cuproptosis, a novel cell death pathway, impacts breast cancer progression and immunotherapy response. A new scoring system using cuproptosis-related genes predicts patient prognosis and immune infiltration, aiding treatment strategies.
Area of Science:
- Cell Biology
- Oncology
- Immunology
Background:
- Cuproptosis is a newly identified programmed cell death mechanism linked to copper overload and mitochondrial dysfunction.
- The efficacy of immunotherapy in breast cancer hinges on the tumor microenvironment's immune cell dynamics.
- The role of cuproptosis-related genes (CRGs) in breast cancer prognosis and immune response is not well understood.
Purpose of the Study:
- To investigate the role of cuproptosis-related genes in breast cancer (BRCA) progression.
- To explore the association between cuproptosis patterns and immune cell infiltration.
- To evaluate the impact of cuproptosis on immunotherapy response in breast cancer.
Main Methods:
- Systematic evaluation of 12 cuproptosis-related genes in BRCA patient cohorts.
- Unsupervised clustering to identify cuproptosis subtypes and development of a cuproptosis-related gene scoring system (CRG_score).
- Analysis of correlations between CRG_score, clinicopathological features, immune infiltration, and immunotherapy sensitivity.
Main Results:
- Two distinct CuproptosisClusters were identified, associated with differential prognosis and immune infiltration.
- A validated CRG signature (PGK1, SLC52A2, SEC14L2, RAD23B, SLC16A6, CCL5, MAL2) and scoring system were developed.
- Lower CRG scores correlated with increased immune cell infiltration, immune checkpoint expression, and enhanced immunotherapy sensitivity.
- RAD23B was identified as a potential therapeutic target, linked to poor prognosis and drug resistance.
Conclusions:
- Cuproptosis plays a significant role in regulating breast cancer progression, prognosis, and immune landscape.
- The CRG_score can quantify cuproptosis patterns, offering insights into BRCA advancement.
- This study provides potential targets for novel immunotherapy and chemotherapy strategies in breast cancer.
Background:
Cuproptosis 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.
Methods:
The 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.
Results:
We 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.
Conclusions:
Our 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.
