Prognosis stratification and response to treatment in breast cancer based on one-carbon metabolism-related signature
IntroductionBreast cancer (BC) is the most common malignant tumor in the female population. Despite staging and treatment consensus guidelines, significant heterogeneity exists in BC patients' prognosis and treatment efficacy. Alterations in one-carbon (1C) metabolism are critical for tumor gro...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1288909/full |
| _version_ | 1797366470454280192 |
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| author | Tongxin Zhang Jingyu Liu Meihuan Wang Xiao Liu Jia Qu Huawei Zhang |
| author_facet | Tongxin Zhang Jingyu Liu Meihuan Wang Xiao Liu Jia Qu Huawei Zhang |
| author_sort | Tongxin Zhang |
| collection | DOAJ |
| description | IntroductionBreast cancer (BC) is the most common malignant tumor in the female population. Despite staging and treatment consensus guidelines, significant heterogeneity exists in BC patients' prognosis and treatment efficacy. Alterations in one-carbon (1C) metabolism are critical for tumor growth, but the value of the role of 1C metabolism in BC has not been fully investigated.MethodsTo investigate the prognostic value of 1C metabolism-related genes in BC, 72 1C metabolism-related genes from GSE20685 dataset were used to construct a risk-score model via univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression algorithm, which was validated on three external datasets. Based on the risk score, all BC patients were categorized into high-risk and low-risk groups. The predictive ability of the model in the four datasets was verified by plotting Kaplan-Meier curve and receiver operating characteristic (ROC) curve. The candidate genes were then analyzed in relation to gene mutations, gene enrichment pathways, immune infiltration, immunotherapy, and drug sensitivity.ResultsWe identified a 7-gene 1C metabolism-related signature for prognosis and structured a prognostic model. ROC analysis demonstrated that the model accurately predicted the 2-, 3-, and 5-year overall survival rate of BC patients in the four cohorts. Kaplan-Meier analysis revealed that survival time of high-risk patients was markedly shorter than that of low-risk patients (p < 0.05). Meanwhile, high-risk patients had a higher tumor mutational burden (TMB), enrichment of tumor-associated pathways such as the IL-17 signaling pathway, lower levels of T follicular helper (Tfh) and B cells naive infiltration, and poorer response to immunotherapy. Furthermore, a strong correlation was found between MAT2B and CHKB and immune checkpoints.DiscussionThese findings offer new insights into the effect of 1C metabolism in the onset, progression, and therapy of BC and can be used to assess BC patients' prognosis, study immune infiltration, and develop potentially more effective clinical treatment options. |
| first_indexed | 2024-03-08T17:05:34Z |
| format | Article |
| id | doaj.art-0e633b29a2004f9f82c8d0aa90fbe6f5 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-08T17:05:34Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-0e633b29a2004f9f82c8d0aa90fbe6f52024-01-04T05:09:45ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2024-01-011310.3389/fonc.2023.12889091288909Prognosis stratification and response to treatment in breast cancer based on one-carbon metabolism-related signatureTongxin ZhangJingyu LiuMeihuan WangXiao LiuJia QuHuawei ZhangIntroductionBreast cancer (BC) is the most common malignant tumor in the female population. Despite staging and treatment consensus guidelines, significant heterogeneity exists in BC patients' prognosis and treatment efficacy. Alterations in one-carbon (1C) metabolism are critical for tumor growth, but the value of the role of 1C metabolism in BC has not been fully investigated.MethodsTo investigate the prognostic value of 1C metabolism-related genes in BC, 72 1C metabolism-related genes from GSE20685 dataset were used to construct a risk-score model via univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression algorithm, which was validated on three external datasets. Based on the risk score, all BC patients were categorized into high-risk and low-risk groups. The predictive ability of the model in the four datasets was verified by plotting Kaplan-Meier curve and receiver operating characteristic (ROC) curve. The candidate genes were then analyzed in relation to gene mutations, gene enrichment pathways, immune infiltration, immunotherapy, and drug sensitivity.ResultsWe identified a 7-gene 1C metabolism-related signature for prognosis and structured a prognostic model. ROC analysis demonstrated that the model accurately predicted the 2-, 3-, and 5-year overall survival rate of BC patients in the four cohorts. Kaplan-Meier analysis revealed that survival time of high-risk patients was markedly shorter than that of low-risk patients (p < 0.05). Meanwhile, high-risk patients had a higher tumor mutational burden (TMB), enrichment of tumor-associated pathways such as the IL-17 signaling pathway, lower levels of T follicular helper (Tfh) and B cells naive infiltration, and poorer response to immunotherapy. Furthermore, a strong correlation was found between MAT2B and CHKB and immune checkpoints.DiscussionThese findings offer new insights into the effect of 1C metabolism in the onset, progression, and therapy of BC and can be used to assess BC patients' prognosis, study immune infiltration, and develop potentially more effective clinical treatment options.https://www.frontiersin.org/articles/10.3389/fonc.2023.1288909/fullone-carbon metabolismbreast cancerprognosisimmune cell infiltrationimmunotherapydrug sensitivity |
| spellingShingle | Tongxin Zhang Jingyu Liu Meihuan Wang Xiao Liu Jia Qu Huawei Zhang Prognosis stratification and response to treatment in breast cancer based on one-carbon metabolism-related signature Frontiers in Oncology one-carbon metabolism breast cancer prognosis immune cell infiltration immunotherapy drug sensitivity |
| title | Prognosis stratification and response to treatment in breast cancer based on one-carbon metabolism-related signature |
| title_full | Prognosis stratification and response to treatment in breast cancer based on one-carbon metabolism-related signature |
| title_fullStr | Prognosis stratification and response to treatment in breast cancer based on one-carbon metabolism-related signature |
| title_full_unstemmed | Prognosis stratification and response to treatment in breast cancer based on one-carbon metabolism-related signature |
| title_short | Prognosis stratification and response to treatment in breast cancer based on one-carbon metabolism-related signature |
| title_sort | prognosis stratification and response to treatment in breast cancer based on one carbon metabolism related signature |
| topic | one-carbon metabolism breast cancer prognosis immune cell infiltration immunotherapy drug sensitivity |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1288909/full |
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