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Ferroptosis-Associated Molecular Features to Aid Patient Clinical Prognosis and Therapy Across Human Cancers

Cui, Kaisa and Gong, Liang and Wang, Kang and Wang, Yuanben and Huang, Liuying and Liu, Bingxin and Li, Qilin and Zhang, Qiang and Fei, Bojian and Huang, Zhaohui (2022) Ferroptosis-Associated Molecular Features to Aid Patient Clinical Prognosis and Therapy Across Human Cancers. Frontiers in Immunology, 13 . Art. No. 888757. ISSN 1664-3224. PMCID PMC9266629. doi:10.3389/fimmu.2022.888757. https://resolver.caltech.edu/CaltechAUTHORS:20220722-769256000

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Abstract

Ferroptosis is a new non-apoptotic form that regulates cell death and is mainly dependent on iron-mediated oxidative damage and subsequent cell membrane damage. Ferroptosis may be a potential therapeutic strategy for immunotherapy, chemotherapy, and radiotherapy in human cancers. Numerous studies have analyzed ferroptosis-correlated signatures or genes, but a systematic landscape of associations among tumor ferroptosis, clinical outcomes, tumor microenvironment, and therapies in human cancers is lacking. Here, we developed a relative ferroptosis level (RFL) combined with drive/suppress regulators and validated it in the Gene Expression Omnibus datasets of ferroptotic drug treatment. Based on this effective evaluation method, we classified about 7,000 tumor samples into high and low RFL groups in each cancer type and observed that high RFL cases demonstrate favorable survival outcomes in nine cancer types from The Cancer Genome Atlas. Then, several RFL-correlated candidate genes that have not been reported to be ferroptosis-related were selected and experimentally validated in five cancer cell lines using Erastin treatment. We further showed that both immunostimulatory and immunosuppressive phenotypes were observed in high RFL tumors, suggesting that the consideration of ferroptosis could be a potential strategy in cancer immunotherapy. Moreover, we found that high RFL cases/cells showed responder or sensitivity to chemotherapy and radiotherapy. Our study provides a comprehensive molecular-level understanding of ferroptosis and may have practical implications for clinical cancer therapies, including immunotherapy, chemotherapy, and radiotherapy.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.3389/fimmu.2022.888757DOIArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc9266629/PubMed CentralArticle
Additional Information:© 2022 Cui, Gong, Wang, Wang, Huang, Liu, Li, Zhang, Fei and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Received: 03 March 2022; Accepted: 19 May 2022; Published: 20 June 2022. We acknowledge the TCGA, GEO, and CPTAC projects. We would like to thank the developers of each method/package used in this study. This work was supported by grants from the National Natural Science Foundation of China (82002550 and 82173063), the Wuxi Health Commission Project (Q202051), and the Wuxi Medical Innovation Team (CXTP003). Author Contributions. KC, LG, KW, and ZH designed the study. KC, LG, KW, BL, and QL performed bioinformatics analyses, proofread and visualization. KC, LG, KW, YW, and LH performed wet-lab experiments. QZ and BF provided conceptual advice. KC, LG, KW, and ZH wrote the manuscript with comments from all authors. All authors discussed the results. All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication. Data Availability Statement. The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Funders:
Funding AgencyGrant Number
National Natural Science Foundation of China82002550
National Natural Science Foundation of China82173063
Wuxi Health CommissionQ202051
Wuxi Medical Innovation TeamCXTP003
Subject Keywords:ferroptosis, cancer, survival, tumor microenvironment, cancer therapy
PubMed Central ID:PMC9266629
DOI:10.3389/fimmu.2022.888757
Record Number:CaltechAUTHORS:20220722-769256000
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20220722-769256000
Official Citation:Cui K, Gong L, Wang K, Wang Y, Huang L, Liu B, Li Q, Zhang Q, Fei B and Huang Z (2022) Ferroptosis-Associated Molecular Features to Aid Patient Clinical Prognosis and Therapy Across Human Cancers. Front. Immunol. 13:888757. doi: 10.3389/fimmu.2022.888757
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:115789
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:25 Jul 2022 16:33
Last Modified:25 Jul 2022 16:33

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