A ferroptosis-associated gene signature for the prediction of prognosis and therapeutic response in luminal-type breast carcinoma
Abstract Ferroptosis is a new form of regulated cell death (RCD), and its emergence has provided a new approach to the progression and drug resistance of breast cancer (BRCA). However, there is still a great gap in the study of ferroptosis-related genes in BRCA, especially luminal-type BRCA patients...
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Nature Portfolio
2021
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oai:doaj.org-article:70cab5ca24ec46188e067a7398cf9acc2021-12-02T16:38:48ZA ferroptosis-associated gene signature for the prediction of prognosis and therapeutic response in luminal-type breast carcinoma10.1038/s41598-021-97102-z2045-2322https://doaj.org/article/70cab5ca24ec46188e067a7398cf9acc2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97102-zhttps://doaj.org/toc/2045-2322Abstract Ferroptosis is a new form of regulated cell death (RCD), and its emergence has provided a new approach to the progression and drug resistance of breast cancer (BRCA). However, there is still a great gap in the study of ferroptosis-related genes in BRCA, especially luminal-type BRCA patients. We downloaded the mRNA expression profiles and corresponding clinical data of BRCA patients from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) databases. Then, we built a prognostic multigene signature with ferroptosis-related differentially expressed genes (DEGs) in the METABRIC cohort and validated it in the TCGA cohort. The predictive value of this signature was investigated in terms of the immune microenvironment and the probability of a response to immunotherapy and chemotherapy. The patients were divided into a high-risk group and a low-risk group according to the ferroptosis-associated gene signature, and the high-risk group had a worse overall survival (OS). The risk score based on the 10 ferroptosis-related gene-based signature was determined to be an independent prognostic predictor in both the METABRIC and TCGA cohorts (HR, 1.41, 95% CI, 1.14–1.76, P = 0.002; HR, 2.19, 95% CI, 1.13–4.26, P = 0.02). Gene set enrichment analysis indicated that the term “cytokine-cytokine receptor interaction” was enriched in the high-risk score subgroup. Moreover, the immune infiltration scores of most immune cells were significantly different between the two groups, the low-risk group was much more sensitive to immunotherapy, and six drugs might have potential therapeutic implications in the high-risk group. Finally, a nomogram incorporating a classifier based on the 10 ferroptosis-related genes, tumor stage, age and histologic grade was established. This nomogram showed favorable discriminative ability and could help guide clinical decision-making for luminal-type breast carcinoma.Yang PengHaochen YuYingzi ZhangFanli QuZhenrong TangChi QuJiao TianBeige ZongYu WangHaoyu RenShengchun LiuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021) |
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Medicine R Science Q Yang Peng Haochen Yu Yingzi Zhang Fanli Qu Zhenrong Tang Chi Qu Jiao Tian Beige Zong Yu Wang Haoyu Ren Shengchun Liu A ferroptosis-associated gene signature for the prediction of prognosis and therapeutic response in luminal-type breast carcinoma |
| description |
Abstract Ferroptosis is a new form of regulated cell death (RCD), and its emergence has provided a new approach to the progression and drug resistance of breast cancer (BRCA). However, there is still a great gap in the study of ferroptosis-related genes in BRCA, especially luminal-type BRCA patients. We downloaded the mRNA expression profiles and corresponding clinical data of BRCA patients from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) databases. Then, we built a prognostic multigene signature with ferroptosis-related differentially expressed genes (DEGs) in the METABRIC cohort and validated it in the TCGA cohort. The predictive value of this signature was investigated in terms of the immune microenvironment and the probability of a response to immunotherapy and chemotherapy. The patients were divided into a high-risk group and a low-risk group according to the ferroptosis-associated gene signature, and the high-risk group had a worse overall survival (OS). The risk score based on the 10 ferroptosis-related gene-based signature was determined to be an independent prognostic predictor in both the METABRIC and TCGA cohorts (HR, 1.41, 95% CI, 1.14–1.76, P = 0.002; HR, 2.19, 95% CI, 1.13–4.26, P = 0.02). Gene set enrichment analysis indicated that the term “cytokine-cytokine receptor interaction” was enriched in the high-risk score subgroup. Moreover, the immune infiltration scores of most immune cells were significantly different between the two groups, the low-risk group was much more sensitive to immunotherapy, and six drugs might have potential therapeutic implications in the high-risk group. Finally, a nomogram incorporating a classifier based on the 10 ferroptosis-related genes, tumor stage, age and histologic grade was established. This nomogram showed favorable discriminative ability and could help guide clinical decision-making for luminal-type breast carcinoma. |
| format |
article |
| author |
Yang Peng Haochen Yu Yingzi Zhang Fanli Qu Zhenrong Tang Chi Qu Jiao Tian Beige Zong Yu Wang Haoyu Ren Shengchun Liu |
| author_facet |
Yang Peng Haochen Yu Yingzi Zhang Fanli Qu Zhenrong Tang Chi Qu Jiao Tian Beige Zong Yu Wang Haoyu Ren Shengchun Liu |
| author_sort |
Yang Peng |
| title |
A ferroptosis-associated gene signature for the prediction of prognosis and therapeutic response in luminal-type breast carcinoma |
| title_short |
A ferroptosis-associated gene signature for the prediction of prognosis and therapeutic response in luminal-type breast carcinoma |
| title_full |
A ferroptosis-associated gene signature for the prediction of prognosis and therapeutic response in luminal-type breast carcinoma |
| title_fullStr |
A ferroptosis-associated gene signature for the prediction of prognosis and therapeutic response in luminal-type breast carcinoma |
| title_full_unstemmed |
A ferroptosis-associated gene signature for the prediction of prognosis and therapeutic response in luminal-type breast carcinoma |
| title_sort |
ferroptosis-associated gene signature for the prediction of prognosis and therapeutic response in luminal-type breast carcinoma |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/70cab5ca24ec46188e067a7398cf9acc |
| work_keys_str_mv |
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