Comprehensive analysis of cuproptosis-related genes and tumor microenvironment infiltration characterization in breast cancer
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...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-10-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.978909/full |
| _version_ | 1797985775113994240 |
|---|---|
| author | Shaoran Song Shaoran Song Miao Zhang Miao Zhang Peiling Xie Shuhong Wang Yaochun Wang Yaochun Wang |
| author_facet | Shaoran Song Shaoran Song Miao Zhang Miao Zhang Peiling Xie Shuhong Wang Yaochun Wang Yaochun Wang |
| author_sort | Shaoran Song |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T07:23:25Z |
| format | Article |
| id | doaj.art-958dbf9d442948fb80013cec31915036 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T07:23:25Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-958dbf9d442948fb80013cec319150362022-12-22T04:37:09ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-10-011310.3389/fimmu.2022.978909978909Comprehensive analysis of cuproptosis-related genes and tumor microenvironment infiltration characterization in breast cancerShaoran Song0Shaoran Song1Miao Zhang2Miao Zhang3Peiling Xie4Shuhong Wang5Yaochun Wang6Yaochun Wang7Center for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaThe Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, ChinaCenter for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaThe Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, ChinaDepartment of Breast Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaCenter for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaThe Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, ChinaBackgroundCuproptosis 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.978909/fullcuproptosisbreast cancercancer molecular subtypestumor microenvironmentimmunotherapy |
| spellingShingle | Shaoran Song Shaoran Song Miao Zhang Miao Zhang Peiling Xie Shuhong Wang Yaochun Wang Yaochun Wang Comprehensive analysis of cuproptosis-related genes and tumor microenvironment infiltration characterization in breast cancer Frontiers in Immunology cuproptosis breast cancer cancer molecular subtypes tumor microenvironment immunotherapy |
| title | Comprehensive analysis of cuproptosis-related genes and tumor microenvironment infiltration characterization in breast cancer |
| title_full | Comprehensive analysis of cuproptosis-related genes and tumor microenvironment infiltration characterization in breast cancer |
| title_fullStr | Comprehensive analysis of cuproptosis-related genes and tumor microenvironment infiltration characterization in breast cancer |
| title_full_unstemmed | Comprehensive analysis of cuproptosis-related genes and tumor microenvironment infiltration characterization in breast cancer |
| title_short | Comprehensive analysis of cuproptosis-related genes and tumor microenvironment infiltration characterization in breast cancer |
| title_sort | comprehensive analysis of cuproptosis related genes and tumor microenvironment infiltration characterization in breast cancer |
| topic | cuproptosis breast cancer cancer molecular subtypes tumor microenvironment immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.978909/full |
| work_keys_str_mv | AT shaoransong comprehensiveanalysisofcuproptosisrelatedgenesandtumormicroenvironmentinfiltrationcharacterizationinbreastcancer AT shaoransong comprehensiveanalysisofcuproptosisrelatedgenesandtumormicroenvironmentinfiltrationcharacterizationinbreastcancer AT miaozhang comprehensiveanalysisofcuproptosisrelatedgenesandtumormicroenvironmentinfiltrationcharacterizationinbreastcancer AT miaozhang comprehensiveanalysisofcuproptosisrelatedgenesandtumormicroenvironmentinfiltrationcharacterizationinbreastcancer AT peilingxie comprehensiveanalysisofcuproptosisrelatedgenesandtumormicroenvironmentinfiltrationcharacterizationinbreastcancer AT shuhongwang comprehensiveanalysisofcuproptosisrelatedgenesandtumormicroenvironmentinfiltrationcharacterizationinbreastcancer AT yaochunwang comprehensiveanalysisofcuproptosisrelatedgenesandtumormicroenvironmentinfiltrationcharacterizationinbreastcancer AT yaochunwang comprehensiveanalysisofcuproptosisrelatedgenesandtumormicroenvironmentinfiltrationcharacterizationinbreastcancer |