Identification of Ferroptosis-Related Prognostic Signature and Subtypes Related to the Immune Microenvironment for Breast Cancer Patients Receiving Neoadjuvant Chemotherapy
PurposeTo identify molecular clusters associated with ferroptosis and to develop a ferroptosis-related signature for providing novel potential targets for the recurrence-free survival and treatment of breast cancer.MethodsFerroptosis-related gene (FRG) signature was constructed by univariate and mul...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.895110/full |
| _version_ | 1818027451044855808 |
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| author | Yuhao Xu Yuhao Xu Yaoqiang Du Qinghui Zheng Tao Zhou Buyun Ye Yihao Wu Qiuran Xu Xuli Meng |
| author_facet | Yuhao Xu Yuhao Xu Yaoqiang Du Qinghui Zheng Tao Zhou Buyun Ye Yihao Wu Qiuran Xu Xuli Meng |
| author_sort | Yuhao Xu |
| collection | DOAJ |
| description | PurposeTo identify molecular clusters associated with ferroptosis and to develop a ferroptosis-related signature for providing novel potential targets for the recurrence-free survival and treatment of breast cancer.MethodsFerroptosis-related gene (FRG) signature was constructed by univariate and multivariate Cox regression and least absolute shrinkage and selection operator (LASSO). Receiver operating characteristic curves, Kaplan–Meier survival analysis, principal component analysis, and univariate and multivariate Cox regression analyses in the training and test cohorts were used to evaluate the application of this signature. Quantitative reverse transcriptase–PCR (qRT-PCR) was employed to detect the expression of FRGs in the model. Furthermore, the correlations between the signature and immune microenvironment, somatic mutation, and chemotherapeutic drugs sensitivity were explored.ResultsInternal and external validations affirmed that relapse-free survival differed significantly between the high-risk and low-risk groups. Univariate and multivariate Cox regression analyses indicated that the riskScore was an independent prognostic factor for BRCA. The areas under the curve (AUCs) for predicting 1-, 2-, and 3-year survival in the training and test cohorts were satisfactory. Significant differences were also found in the immune microenvironment and IC50 of chemotherapeutic drugs between different risk groups. Furthermore, we divided patients into three clusters based on 18 FRGs to ameliorate the situation of immunotherapy failure in BRCA.ConclusionsThe FRG signature functions as a robust prognostic predictor of the immune microenvironment and therapeutic response, with great potential to guide individualized treatment strategies in the future. |
| first_indexed | 2024-12-10T04:48:06Z |
| format | Article |
| id | doaj.art-b5dbf395bdac40c8beb3e231dec74861 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T04:48:06Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b5dbf395bdac40c8beb3e231dec748612022-12-22T02:01:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-05-011310.3389/fimmu.2022.895110895110Identification of Ferroptosis-Related Prognostic Signature and Subtypes Related to the Immune Microenvironment for Breast Cancer Patients Receiving Neoadjuvant ChemotherapyYuhao Xu0Yuhao Xu1Yaoqiang Du2Qinghui Zheng3Tao Zhou4Buyun Ye5Yihao Wu6Qiuran Xu7Xuli Meng8The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, ChinaGeneral Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, ChinaLaboratory Medicine Center, Department of Transfusion Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, ChinaGeneral Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, ChinaHangzhou Medical College, Hangzhou, ChinaThe Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, ChinaCollege of Pharmacy, Zhejiang University of Technology, Hangzhou, ChinaLaboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, ChinaGeneral Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, ChinaPurposeTo identify molecular clusters associated with ferroptosis and to develop a ferroptosis-related signature for providing novel potential targets for the recurrence-free survival and treatment of breast cancer.MethodsFerroptosis-related gene (FRG) signature was constructed by univariate and multivariate Cox regression and least absolute shrinkage and selection operator (LASSO). Receiver operating characteristic curves, Kaplan–Meier survival analysis, principal component analysis, and univariate and multivariate Cox regression analyses in the training and test cohorts were used to evaluate the application of this signature. Quantitative reverse transcriptase–PCR (qRT-PCR) was employed to detect the expression of FRGs in the model. Furthermore, the correlations between the signature and immune microenvironment, somatic mutation, and chemotherapeutic drugs sensitivity were explored.ResultsInternal and external validations affirmed that relapse-free survival differed significantly between the high-risk and low-risk groups. Univariate and multivariate Cox regression analyses indicated that the riskScore was an independent prognostic factor for BRCA. The areas under the curve (AUCs) for predicting 1-, 2-, and 3-year survival in the training and test cohorts were satisfactory. Significant differences were also found in the immune microenvironment and IC50 of chemotherapeutic drugs between different risk groups. Furthermore, we divided patients into three clusters based on 18 FRGs to ameliorate the situation of immunotherapy failure in BRCA.ConclusionsThe FRG signature functions as a robust prognostic predictor of the immune microenvironment and therapeutic response, with great potential to guide individualized treatment strategies in the future.https://www.frontiersin.org/articles/10.3389/fimmu.2022.895110/fullbreast cancerferroptosisrelapse-free survivalneoadjuvant chemotherapyimmune microenvironment |
| spellingShingle | Yuhao Xu Yuhao Xu Yaoqiang Du Qinghui Zheng Tao Zhou Buyun Ye Yihao Wu Qiuran Xu Xuli Meng Identification of Ferroptosis-Related Prognostic Signature and Subtypes Related to the Immune Microenvironment for Breast Cancer Patients Receiving Neoadjuvant Chemotherapy Frontiers in Immunology breast cancer ferroptosis relapse-free survival neoadjuvant chemotherapy immune microenvironment |
| title | Identification of Ferroptosis-Related Prognostic Signature and Subtypes Related to the Immune Microenvironment for Breast Cancer Patients Receiving Neoadjuvant Chemotherapy |
| title_full | Identification of Ferroptosis-Related Prognostic Signature and Subtypes Related to the Immune Microenvironment for Breast Cancer Patients Receiving Neoadjuvant Chemotherapy |
| title_fullStr | Identification of Ferroptosis-Related Prognostic Signature and Subtypes Related to the Immune Microenvironment for Breast Cancer Patients Receiving Neoadjuvant Chemotherapy |
| title_full_unstemmed | Identification of Ferroptosis-Related Prognostic Signature and Subtypes Related to the Immune Microenvironment for Breast Cancer Patients Receiving Neoadjuvant Chemotherapy |
| title_short | Identification of Ferroptosis-Related Prognostic Signature and Subtypes Related to the Immune Microenvironment for Breast Cancer Patients Receiving Neoadjuvant Chemotherapy |
| title_sort | identification of ferroptosis related prognostic signature and subtypes related to the immune microenvironment for breast cancer patients receiving neoadjuvant chemotherapy |
| topic | breast cancer ferroptosis relapse-free survival neoadjuvant chemotherapy immune microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.895110/full |
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