Identification of molecular subtypes and a six-gene risk model related to cuproptosis for triple negative breast cancer
Background: Breast cancer is the mostly diagnosed cancer worldwide, and triple negative breast cancer (TNBC) has the worst prognosis. Cuproptosis is a newly identified form of cell death, whose mechanism has not been fully explored in TNBC. This study thought to unveil the potential association betw...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.1022236/full |
| _version_ | 1811336049733926912 |
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| author | Baoxi Zhu Songping Wang Rui Wang Xiaoliang Wang |
| author_facet | Baoxi Zhu Songping Wang Rui Wang Xiaoliang Wang |
| author_sort | Baoxi Zhu |
| collection | DOAJ |
| description | Background: Breast cancer is the mostly diagnosed cancer worldwide, and triple negative breast cancer (TNBC) has the worst prognosis. Cuproptosis is a newly identified form of cell death, whose mechanism has not been fully explored in TNBC. This study thought to unveil the potential association between cuproptosis and TNBC.Materials and Methods: Gene expression files with clinical data of TNBC downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were included in this study. Consensus clustering was utilized to perform molecular subtyping based on cuproptosis-associated genes. Limma package was applied to distinguish differentially expressed genes. Univariate Cox regression was used to identify prognostic genes. Least absolute shrinkage and selection operator and stepwise Akaike information criterion optimized and established a risk model.Results: We constructed three molecular subtypes based on cuproptosis-associated genes, and the cuproptosis-based subtyping showed a robustness in different datasets. Clust2 showed the worst prognosis and immune-related pathways such as chemokine signaling pathway were significantly activated in clust2. Clust2 also exhibited a high possibility of immune escape to immune checkpoint blockade. In addition, a six-gene risk model was established manifesting a high AUC score over 0.85 in TCGA dataset. High- and low-risk groups had distinct prognosis and immune infiltration. Finally, a nomogram was constructed with strong performance in predicting TNBC prognosis than the staging system.Conclusion: The molecular subtyping system related to cuproptosis had a potential in guiding immunotherapy for TNBC patients. Importantly, the six-gene risk model was effective and reliable to predict TNBC prognosis. |
| first_indexed | 2024-04-13T17:33:40Z |
| format | Article |
| id | doaj.art-d5d2c6db494c4ef1b3f04a56f1108bdd |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-13T17:33:40Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-d5d2c6db494c4ef1b3f04a56f1108bdd2022-12-22T02:37:29ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-10-011310.3389/fgene.2022.10222361022236Identification of molecular subtypes and a six-gene risk model related to cuproptosis for triple negative breast cancerBaoxi ZhuSongping WangRui WangXiaoliang WangBackground: Breast cancer is the mostly diagnosed cancer worldwide, and triple negative breast cancer (TNBC) has the worst prognosis. Cuproptosis is a newly identified form of cell death, whose mechanism has not been fully explored in TNBC. This study thought to unveil the potential association between cuproptosis and TNBC.Materials and Methods: Gene expression files with clinical data of TNBC downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were included in this study. Consensus clustering was utilized to perform molecular subtyping based on cuproptosis-associated genes. Limma package was applied to distinguish differentially expressed genes. Univariate Cox regression was used to identify prognostic genes. Least absolute shrinkage and selection operator and stepwise Akaike information criterion optimized and established a risk model.Results: We constructed three molecular subtypes based on cuproptosis-associated genes, and the cuproptosis-based subtyping showed a robustness in different datasets. Clust2 showed the worst prognosis and immune-related pathways such as chemokine signaling pathway were significantly activated in clust2. Clust2 also exhibited a high possibility of immune escape to immune checkpoint blockade. In addition, a six-gene risk model was established manifesting a high AUC score over 0.85 in TCGA dataset. High- and low-risk groups had distinct prognosis and immune infiltration. Finally, a nomogram was constructed with strong performance in predicting TNBC prognosis than the staging system.Conclusion: The molecular subtyping system related to cuproptosis had a potential in guiding immunotherapy for TNBC patients. Importantly, the six-gene risk model was effective and reliable to predict TNBC prognosis.https://www.frontiersin.org/articles/10.3389/fgene.2022.1022236/fulltriple negative breast cancercuproptosismolecular subtypesrisk modelSIX-gene |
| spellingShingle | Baoxi Zhu Songping Wang Rui Wang Xiaoliang Wang Identification of molecular subtypes and a six-gene risk model related to cuproptosis for triple negative breast cancer Frontiers in Genetics triple negative breast cancer cuproptosis molecular subtypes risk model SIX-gene |
| title | Identification of molecular subtypes and a six-gene risk model related to cuproptosis for triple negative breast cancer |
| title_full | Identification of molecular subtypes and a six-gene risk model related to cuproptosis for triple negative breast cancer |
| title_fullStr | Identification of molecular subtypes and a six-gene risk model related to cuproptosis for triple negative breast cancer |
| title_full_unstemmed | Identification of molecular subtypes and a six-gene risk model related to cuproptosis for triple negative breast cancer |
| title_short | Identification of molecular subtypes and a six-gene risk model related to cuproptosis for triple negative breast cancer |
| title_sort | identification of molecular subtypes and a six gene risk model related to cuproptosis for triple negative breast cancer |
| topic | triple negative breast cancer cuproptosis molecular subtypes risk model SIX-gene |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.1022236/full |
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