Quantification of ferroptosis pathway status revealed heterogeneity in breast cancer patients with distinct immune microenvironment
Clinical significance and biological functions of the ferroptosis pathway were addressed in all aspect of cancer regarding multi-omics level; however, the overall status of ferroptosis pathway alteration was hard to evaluate. The aim of this study is to comprehensively analyze the putative biologica...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.956999/full |
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| author | Yuying Li Yuying Li Tianfu Li Tianfu Li Duanyang Zhai Duanyang Zhai Chuanbo Xie Xiaying Kuang Ying Lin Nan Shao |
| author_facet | Yuying Li Yuying Li Tianfu Li Tianfu Li Duanyang Zhai Duanyang Zhai Chuanbo Xie Xiaying Kuang Ying Lin Nan Shao |
| author_sort | Yuying Li |
| collection | DOAJ |
| description | Clinical significance and biological functions of the ferroptosis pathway were addressed in all aspect of cancer regarding multi-omics level; however, the overall status of ferroptosis pathway alteration was hard to evaluate. The aim of this study is to comprehensively analyze the putative biological, pathological, and clinical functions of the ferroptosis pathway in breast cancer on a pathway level. By adopting the bioinformatic algorithm “pathifier”, we quantified five programmed cell death (PCD) pathways (KO04210 Apoptosis; KO04216 Ferroptosis; KO04217 Necroptosis; GO:0070269 Pyroptosis; GO:0048102 Autophagic cell death) in breast cancer patients, and we featured the clinical characteristics and prognostic value of each pathway in breast cancer and found significantly activated PCD in cancer patients, among which ferroptosis demonstrated a significant correlation with the prognosis of breast cancer. Correlation analysis between PCD pathways identified intra-tumor heterogeneity of breast cancer. Therefore, clustering of patients based on the status of PCD pathways was done. Comparisons between subgroups highlighted specifically activated ferroptosis in cluster 2 patients, which showed the distinct status of tumor immunity and microenvironment from other clusters, indicating putative correlations with ferroptosis. NDUFA13 was identified and selected as a putative biomarker for cluster 2 patients. Experimental validations were executed on cellular level and NDUFA13 showed an important role in regulating ferroptosis activation and can work as a biomarker for ferroptosis pathway status. In conclusion, the status of the ferroptosis pathway significantly correlated with the clinical outcomes and intra-tumor heterogeneity of breast cancer, and NDUFA13 expression was identified as a positive biomarker for ferroptosis pathway activation in breast cancer patients. |
| first_indexed | 2024-04-11T13:19:25Z |
| format | Article |
| id | doaj.art-a32d9fbd682f40829524213dcd945341 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-11T13:19:25Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-a32d9fbd682f40829524213dcd9453412022-12-22T04:22:15ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-09-011210.3389/fonc.2022.956999956999Quantification of ferroptosis pathway status revealed heterogeneity in breast cancer patients with distinct immune microenvironmentYuying Li0Yuying Li1Tianfu Li2Tianfu Li3Duanyang Zhai4Duanyang Zhai5Chuanbo Xie6Xiaying Kuang7Ying Lin8Nan Shao9Breast Disease Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaLaboratory of Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaBreast Disease Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaLaboratory of Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaBreast Disease Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaLaboratory of Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaCancer Prevention Center, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, ChinaBreast Disease Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaBreast Disease Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaBreast Disease Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaClinical significance and biological functions of the ferroptosis pathway were addressed in all aspect of cancer regarding multi-omics level; however, the overall status of ferroptosis pathway alteration was hard to evaluate. The aim of this study is to comprehensively analyze the putative biological, pathological, and clinical functions of the ferroptosis pathway in breast cancer on a pathway level. By adopting the bioinformatic algorithm “pathifier”, we quantified five programmed cell death (PCD) pathways (KO04210 Apoptosis; KO04216 Ferroptosis; KO04217 Necroptosis; GO:0070269 Pyroptosis; GO:0048102 Autophagic cell death) in breast cancer patients, and we featured the clinical characteristics and prognostic value of each pathway in breast cancer and found significantly activated PCD in cancer patients, among which ferroptosis demonstrated a significant correlation with the prognosis of breast cancer. Correlation analysis between PCD pathways identified intra-tumor heterogeneity of breast cancer. Therefore, clustering of patients based on the status of PCD pathways was done. Comparisons between subgroups highlighted specifically activated ferroptosis in cluster 2 patients, which showed the distinct status of tumor immunity and microenvironment from other clusters, indicating putative correlations with ferroptosis. NDUFA13 was identified and selected as a putative biomarker for cluster 2 patients. Experimental validations were executed on cellular level and NDUFA13 showed an important role in regulating ferroptosis activation and can work as a biomarker for ferroptosis pathway status. In conclusion, the status of the ferroptosis pathway significantly correlated with the clinical outcomes and intra-tumor heterogeneity of breast cancer, and NDUFA13 expression was identified as a positive biomarker for ferroptosis pathway activation in breast cancer patients.https://www.frontiersin.org/articles/10.3389/fonc.2022.956999/fullprogrammed cell deathferroptosistumor microenvironmentheterogeneityNDUFA13 |
| spellingShingle | Yuying Li Yuying Li Tianfu Li Tianfu Li Duanyang Zhai Duanyang Zhai Chuanbo Xie Xiaying Kuang Ying Lin Nan Shao Quantification of ferroptosis pathway status revealed heterogeneity in breast cancer patients with distinct immune microenvironment Frontiers in Oncology programmed cell death ferroptosis tumor microenvironment heterogeneity NDUFA13 |
| title | Quantification of ferroptosis pathway status revealed heterogeneity in breast cancer patients with distinct immune microenvironment |
| title_full | Quantification of ferroptosis pathway status revealed heterogeneity in breast cancer patients with distinct immune microenvironment |
| title_fullStr | Quantification of ferroptosis pathway status revealed heterogeneity in breast cancer patients with distinct immune microenvironment |
| title_full_unstemmed | Quantification of ferroptosis pathway status revealed heterogeneity in breast cancer patients with distinct immune microenvironment |
| title_short | Quantification of ferroptosis pathway status revealed heterogeneity in breast cancer patients with distinct immune microenvironment |
| title_sort | quantification of ferroptosis pathway status revealed heterogeneity in breast cancer patients with distinct immune microenvironment |
| topic | programmed cell death ferroptosis tumor microenvironment heterogeneity NDUFA13 |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.956999/full |
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