Multi-omics analysis reveals that neutrophil extracellular traps related gene TIMP1 promotes CRC progression and influences ferroptosis
Abstract Background Previous studies have found that neutrophil extracellular traps (NETs) are highly expressed in colorectal cancer (CRC) and are associated with poor prognosis. Currently, there are few studies on the relationship between NETs and CRC, so we tried to explore new markers based on NE...
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| Format: | Article |
| Language: | English |
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BMC
2025-01-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-025-03643-y |
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| author | Yuzhao Jin Luyu Liao Qianping Chen Bufu Tang Jin Jiang Ji Zhu Minghua Bai |
| author_facet | Yuzhao Jin Luyu Liao Qianping Chen Bufu Tang Jin Jiang Ji Zhu Minghua Bai |
| author_sort | Yuzhao Jin |
| collection | DOAJ |
| description | Abstract Background Previous studies have found that neutrophil extracellular traps (NETs) are highly expressed in colorectal cancer (CRC) and are associated with poor prognosis. Currently, there are few studies on the relationship between NETs and CRC, so we tried to explore new markers based on NETs to assist in the treatment of CRC. Method We jointly screened three major NETs genes through machine learning. Large-sample RNA transcriptome and single-cell transcriptome analysis further confirmed that TIMP1 is a core gene in NETs. We used small interfering RNA to knockdown TIMP1, and verified the ability of TIMP1 in CRC proliferation, invasion and migration through western blot, transwell, cell scratch assay, cell clone formation and other experiments. Result We screened out three major NETs Genes: TIMP1, F3, and CRISPLD2 based on machine learning. The NETs score constructed based on this not only predicts the prognosis of CRC patients but also shows significant differences in MSI status, chenckpoints expression, and predicted efficacy of PD-L1 targeted therapy. Transcriptome and single-cell data reveal that TIMP1 is highly expressed in neutrophils and is associated with poor prognosis in colorectal cancer patients and the occurrence of ferroptosis. Biological experiments have proven that TIMP1 can promote the proliferation, invasion and migration of CRC. Conclude Bioinformatics analysis combined with experimental verification showed that TIMP1 is related to ferroptosis and plays a promoting role in the invasion, migration and proliferation of CRC. |
| format | Article |
| id | doaj-art-a12f05819d7049ea93ea21625787b7f8 |
| institution | Kabale University |
| issn | 1475-2867 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj-art-a12f05819d7049ea93ea21625787b7f82025-02-02T12:43:24ZengBMCCancer Cell International1475-28672025-01-0125111710.1186/s12935-025-03643-yMulti-omics analysis reveals that neutrophil extracellular traps related gene TIMP1 promotes CRC progression and influences ferroptosisYuzhao Jin0Luyu Liao1Qianping Chen2Bufu Tang3Jin Jiang4Ji Zhu5Minghua Bai6Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital)Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital)Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital)Department of Radiation Oncology, Zhongshan Hospital, Fudan UniversityDepartment of Oncology, Affiliated Hospital of Jiaxing University, The First Hospital of JiaxingPostgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital)Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital)Abstract Background Previous studies have found that neutrophil extracellular traps (NETs) are highly expressed in colorectal cancer (CRC) and are associated with poor prognosis. Currently, there are few studies on the relationship between NETs and CRC, so we tried to explore new markers based on NETs to assist in the treatment of CRC. Method We jointly screened three major NETs genes through machine learning. Large-sample RNA transcriptome and single-cell transcriptome analysis further confirmed that TIMP1 is a core gene in NETs. We used small interfering RNA to knockdown TIMP1, and verified the ability of TIMP1 in CRC proliferation, invasion and migration through western blot, transwell, cell scratch assay, cell clone formation and other experiments. Result We screened out three major NETs Genes: TIMP1, F3, and CRISPLD2 based on machine learning. The NETs score constructed based on this not only predicts the prognosis of CRC patients but also shows significant differences in MSI status, chenckpoints expression, and predicted efficacy of PD-L1 targeted therapy. Transcriptome and single-cell data reveal that TIMP1 is highly expressed in neutrophils and is associated with poor prognosis in colorectal cancer patients and the occurrence of ferroptosis. Biological experiments have proven that TIMP1 can promote the proliferation, invasion and migration of CRC. Conclude Bioinformatics analysis combined with experimental verification showed that TIMP1 is related to ferroptosis and plays a promoting role in the invasion, migration and proliferation of CRC.https://doi.org/10.1186/s12935-025-03643-yNeutrophil extracellular trapsCRCTIMP1Ferroptosis |
| spellingShingle | Yuzhao Jin Luyu Liao Qianping Chen Bufu Tang Jin Jiang Ji Zhu Minghua Bai Multi-omics analysis reveals that neutrophil extracellular traps related gene TIMP1 promotes CRC progression and influences ferroptosis Cancer Cell International Neutrophil extracellular traps CRC TIMP1 Ferroptosis |
| title | Multi-omics analysis reveals that neutrophil extracellular traps related gene TIMP1 promotes CRC progression and influences ferroptosis |
| title_full | Multi-omics analysis reveals that neutrophil extracellular traps related gene TIMP1 promotes CRC progression and influences ferroptosis |
| title_fullStr | Multi-omics analysis reveals that neutrophil extracellular traps related gene TIMP1 promotes CRC progression and influences ferroptosis |
| title_full_unstemmed | Multi-omics analysis reveals that neutrophil extracellular traps related gene TIMP1 promotes CRC progression and influences ferroptosis |
| title_short | Multi-omics analysis reveals that neutrophil extracellular traps related gene TIMP1 promotes CRC progression and influences ferroptosis |
| title_sort | multi omics analysis reveals that neutrophil extracellular traps related gene timp1 promotes crc progression and influences ferroptosis |
| topic | Neutrophil extracellular traps CRC TIMP1 Ferroptosis |
| url | https://doi.org/10.1186/s12935-025-03643-y |
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