Development and validation of a combined hypoxia and ferroptosis prognostic signature for breast cancer
BackgroundHypoxia is involved in tumor biological processes and disease progression. Ferroptosis, as a newly discovered programmed cell death process, is closely related to breast cancer (BC) occurrence and development. However, reliable prognostic signatures based on a combination of hypoxia and fe...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-03-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1077342/full |
| _version_ | 1797871363995729920 |
|---|---|
| author | Jianxin Zhong Xi Shen Junjie Zhou Heping Yu Birong Wang Jianbin Sun Jing Wang Feng Liu |
| author_facet | Jianxin Zhong Xi Shen Junjie Zhou Heping Yu Birong Wang Jianbin Sun Jing Wang Feng Liu |
| author_sort | Jianxin Zhong |
| collection | DOAJ |
| description | BackgroundHypoxia is involved in tumor biological processes and disease progression. Ferroptosis, as a newly discovered programmed cell death process, is closely related to breast cancer (BC) occurrence and development. However, reliable prognostic signatures based on a combination of hypoxia and ferroptosis in BC have not been developed.MethodWe set The Cancer Genome Atlas (TCGA) breast cancer cohort as training set and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) BC cohort as the validation set. Least Absolute Shrinkage and Selection Operator (LASSO) and COX regression approaches were used to construct ferroptosis-related genes (FRGs) and hypoxia-related genes (HRGs) prognostic signature (HFRS). The CIBERSORT algorithm and ESTIMATE score were used to explore the relationship between HFRS and tumor immune microenvironment. Immunohistochemical staining was used to detect protein expression in tissue samples. A nomogram was developed to advance the clinical application of HFRS signature.ResultsTen ferroptosis-related genes and hypoxia-related genes were screened to construct the HFRS prognostic signature in TCGA BC cohort, and the predictive capacity was verified in METABRIC BC cohort. BC patients with high-HFRS had shorter survival time, higher tumor stage, and a higher rate of positive lymph node. Moreover, high HFRS was associated with high hypoxia, ferroptosis, and immunosuppression status. A nomogram that was constructed with age, stage, and HFRS signature showed a strong prognostic capability to predict overall survival (OS) for BC patients.ConclusionWe developed a novel prognostic model with hypoxia and ferroptosis-related genes to predict OS, and characterize the immune microenvironment of BC patients, which might provide new cures for clinical decision-making and individual treatment of BC patients. |
| first_indexed | 2024-04-10T00:42:45Z |
| format | Article |
| id | doaj.art-4c51042c8e5840b6b6eb00bcca30f251 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-10T00:42:45Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-4c51042c8e5840b6b6eb00bcca30f2512023-03-14T05:30:04ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-03-011310.3389/fonc.2023.10773421077342Development and validation of a combined hypoxia and ferroptosis prognostic signature for breast cancerJianxin Zhong0Xi Shen1Junjie Zhou2Heping Yu3Birong Wang4Jianbin Sun5Jing Wang6Feng Liu7Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Breast Oncology, Peking University Cancer Hospital and Institute, Beijing, ChinaDepartment of Head and Neck Oncology and Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Thyroid and Breast Surgery, Wuhan Fourth Hospital, Wuhan, ChinaDepartment of Thyroid and Breast Surgery, Wuhan Fourth Hospital, Wuhan, ChinaDepartment of Thyroid and Breast Surgery, Wuhan Fourth Hospital, Wuhan, ChinaDepartment of Thoracic Surgery, Wuhan Fourth Hospital, Wuhan, ChinaDepartment of Thyroid and Breast Surgery, Wuhan Fourth Hospital, Wuhan, ChinaBackgroundHypoxia is involved in tumor biological processes and disease progression. Ferroptosis, as a newly discovered programmed cell death process, is closely related to breast cancer (BC) occurrence and development. However, reliable prognostic signatures based on a combination of hypoxia and ferroptosis in BC have not been developed.MethodWe set The Cancer Genome Atlas (TCGA) breast cancer cohort as training set and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) BC cohort as the validation set. Least Absolute Shrinkage and Selection Operator (LASSO) and COX regression approaches were used to construct ferroptosis-related genes (FRGs) and hypoxia-related genes (HRGs) prognostic signature (HFRS). The CIBERSORT algorithm and ESTIMATE score were used to explore the relationship between HFRS and tumor immune microenvironment. Immunohistochemical staining was used to detect protein expression in tissue samples. A nomogram was developed to advance the clinical application of HFRS signature.ResultsTen ferroptosis-related genes and hypoxia-related genes were screened to construct the HFRS prognostic signature in TCGA BC cohort, and the predictive capacity was verified in METABRIC BC cohort. BC patients with high-HFRS had shorter survival time, higher tumor stage, and a higher rate of positive lymph node. Moreover, high HFRS was associated with high hypoxia, ferroptosis, and immunosuppression status. A nomogram that was constructed with age, stage, and HFRS signature showed a strong prognostic capability to predict overall survival (OS) for BC patients.ConclusionWe developed a novel prognostic model with hypoxia and ferroptosis-related genes to predict OS, and characterize the immune microenvironment of BC patients, which might provide new cures for clinical decision-making and individual treatment of BC patients.https://www.frontiersin.org/articles/10.3389/fonc.2023.1077342/fullhypoxiaferroptosisprognostic modelbreast cancertumor microenvironment |
| spellingShingle | Jianxin Zhong Xi Shen Junjie Zhou Heping Yu Birong Wang Jianbin Sun Jing Wang Feng Liu Development and validation of a combined hypoxia and ferroptosis prognostic signature for breast cancer Frontiers in Oncology hypoxia ferroptosis prognostic model breast cancer tumor microenvironment |
| title | Development and validation of a combined hypoxia and ferroptosis prognostic signature for breast cancer |
| title_full | Development and validation of a combined hypoxia and ferroptosis prognostic signature for breast cancer |
| title_fullStr | Development and validation of a combined hypoxia and ferroptosis prognostic signature for breast cancer |
| title_full_unstemmed | Development and validation of a combined hypoxia and ferroptosis prognostic signature for breast cancer |
| title_short | Development and validation of a combined hypoxia and ferroptosis prognostic signature for breast cancer |
| title_sort | development and validation of a combined hypoxia and ferroptosis prognostic signature for breast cancer |
| topic | hypoxia ferroptosis prognostic model breast cancer tumor microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1077342/full |
| work_keys_str_mv | AT jianxinzhong developmentandvalidationofacombinedhypoxiaandferroptosisprognosticsignatureforbreastcancer AT xishen developmentandvalidationofacombinedhypoxiaandferroptosisprognosticsignatureforbreastcancer AT junjiezhou developmentandvalidationofacombinedhypoxiaandferroptosisprognosticsignatureforbreastcancer AT hepingyu developmentandvalidationofacombinedhypoxiaandferroptosisprognosticsignatureforbreastcancer AT birongwang developmentandvalidationofacombinedhypoxiaandferroptosisprognosticsignatureforbreastcancer AT jianbinsun developmentandvalidationofacombinedhypoxiaandferroptosisprognosticsignatureforbreastcancer AT jingwang developmentandvalidationofacombinedhypoxiaandferroptosisprognosticsignatureforbreastcancer AT fengliu developmentandvalidationofacombinedhypoxiaandferroptosisprognosticsignatureforbreastcancer |