Ferroptosis-disulfidptosis-related CHMP6 is a clinico-immune target in colorectal cancer
Abstract Background Ferroptosis and disulfidptosis are newly discovered forms of regulated cell death that play critical roles in cancer progression, metabolism, and immune evasion. However, their interplay and combined influence on colorectal cancer (CRC) progression remain insufficiently understoo...
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BMC
2025-07-01
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| Series: | Biology Direct |
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| Online Access: | https://doi.org/10.1186/s13062-025-00676-1 |
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| author | Yifei Zhu Huixia Huang Jiayu Chen Keji Chen Yanxi Yao Yaxian Wang Yuxue Li Zhibing Qiu Dawei Li Ping Wei |
| author_facet | Yifei Zhu Huixia Huang Jiayu Chen Keji Chen Yanxi Yao Yaxian Wang Yuxue Li Zhibing Qiu Dawei Li Ping Wei |
| author_sort | Yifei Zhu |
| collection | DOAJ |
| description | Abstract Background Ferroptosis and disulfidptosis are newly discovered forms of regulated cell death that play critical roles in cancer progression, metabolism, and immune evasion. However, their interplay and combined influence on colorectal cancer (CRC) progression remain insufficiently understood. Methods We developed a ferroptosis-disulfidptosis-related gene (FDRG) score using machine-learning algorithms to analyze gene modifications associated with these pathways in CRC, utilizing data from the TCGA and GEO databases. The model was externally validated, and associations with clinical outcomes, immune infiltration, mutational landscapes, immunotherapy responses, and drug sensitivity were explored. Key genes were further investigated through bioinformatics and in vitro experiments. Results We constructed an 8-gene risk model with strong prognostic value, stratifying CRC patients into high- and low-risk groups with significant differences in clinical characteristics, immune cell infiltration, and therapeutic responses. Among these genes, CHMP6 was identified as a previously uncharacterized tumor suppressor in CRC. Beyond its inhibitory effect on tumor cell proliferation, migration, and invasion, CHMP6 was found to play a critical role in modulating anti-tumor immunity. Our findings established CHMP6 as a dual-function tumor suppressor that not only restrains tumor progression but also enhances immune-mediated tumor control. Conclusions The FDRG score is a robust tool for predicting CRC prognosis, tumor microenvironment dynamics, and response to immunotherapy. CHMP6 emerged as a promising tumor suppressor and potential therapeutic target, offering new insights into CRC treatment strategies. |
| format | Article |
| id | doaj-art-e6f92f6e852844c6bb01df4e8ae3f385 |
| institution | DOAJ |
| issn | 1745-6150 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Biology Direct |
| spelling | doaj-art-e6f92f6e852844c6bb01df4e8ae3f3852025-08-20T03:04:35ZengBMCBiology Direct1745-61502025-07-0120111910.1186/s13062-025-00676-1Ferroptosis-disulfidptosis-related CHMP6 is a clinico-immune target in colorectal cancerYifei Zhu0Huixia Huang1Jiayu Chen2Keji Chen3Yanxi Yao4Yaxian Wang5Yuxue Li6Zhibing Qiu7Dawei Li8Ping Wei9Department of Oncology, Shanghai Medical College of Fudan UniversityDepartment of Oncology, Shanghai Medical College of Fudan UniversityDepartment of Oncology, Shanghai Medical College of Fudan UniversityDepartment of Oncology, Shanghai Medical College of Fudan UniversityDepartment of Oncology, Shanghai Medical College of Fudan UniversityDepartment of Oncology, Shanghai Medical College of Fudan UniversityDepartment of Oncology, Shanghai Medical College of Fudan UniversityDepartment of Digestive Disease, Huashan Hospital, Fudan UniversityDepartment of Oncology, Shanghai Medical College of Fudan UniversityDepartment of Oncology, Shanghai Medical College of Fudan UniversityAbstract Background Ferroptosis and disulfidptosis are newly discovered forms of regulated cell death that play critical roles in cancer progression, metabolism, and immune evasion. However, their interplay and combined influence on colorectal cancer (CRC) progression remain insufficiently understood. Methods We developed a ferroptosis-disulfidptosis-related gene (FDRG) score using machine-learning algorithms to analyze gene modifications associated with these pathways in CRC, utilizing data from the TCGA and GEO databases. The model was externally validated, and associations with clinical outcomes, immune infiltration, mutational landscapes, immunotherapy responses, and drug sensitivity were explored. Key genes were further investigated through bioinformatics and in vitro experiments. Results We constructed an 8-gene risk model with strong prognostic value, stratifying CRC patients into high- and low-risk groups with significant differences in clinical characteristics, immune cell infiltration, and therapeutic responses. Among these genes, CHMP6 was identified as a previously uncharacterized tumor suppressor in CRC. Beyond its inhibitory effect on tumor cell proliferation, migration, and invasion, CHMP6 was found to play a critical role in modulating anti-tumor immunity. Our findings established CHMP6 as a dual-function tumor suppressor that not only restrains tumor progression but also enhances immune-mediated tumor control. Conclusions The FDRG score is a robust tool for predicting CRC prognosis, tumor microenvironment dynamics, and response to immunotherapy. CHMP6 emerged as a promising tumor suppressor and potential therapeutic target, offering new insights into CRC treatment strategies.https://doi.org/10.1186/s13062-025-00676-1FerroptosisDisulfidptosisColorectal cancerTumor microenvironmentImmunotherapyDrug sensitivity |
| spellingShingle | Yifei Zhu Huixia Huang Jiayu Chen Keji Chen Yanxi Yao Yaxian Wang Yuxue Li Zhibing Qiu Dawei Li Ping Wei Ferroptosis-disulfidptosis-related CHMP6 is a clinico-immune target in colorectal cancer Biology Direct Ferroptosis Disulfidptosis Colorectal cancer Tumor microenvironment Immunotherapy Drug sensitivity |
| title | Ferroptosis-disulfidptosis-related CHMP6 is a clinico-immune target in colorectal cancer |
| title_full | Ferroptosis-disulfidptosis-related CHMP6 is a clinico-immune target in colorectal cancer |
| title_fullStr | Ferroptosis-disulfidptosis-related CHMP6 is a clinico-immune target in colorectal cancer |
| title_full_unstemmed | Ferroptosis-disulfidptosis-related CHMP6 is a clinico-immune target in colorectal cancer |
| title_short | Ferroptosis-disulfidptosis-related CHMP6 is a clinico-immune target in colorectal cancer |
| title_sort | ferroptosis disulfidptosis related chmp6 is a clinico immune target in colorectal cancer |
| topic | Ferroptosis Disulfidptosis Colorectal cancer Tumor microenvironment Immunotherapy Drug sensitivity |
| url | https://doi.org/10.1186/s13062-025-00676-1 |
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