A neutrophil extracellular traps-related classification predicts prognosis and response to immunotherapy in colon cancer
Abstract Neutrophil extracellular traps (NETs) have been categorized as a form of inflammatory cell death mode of neutrophils (NETosis) involved in natural immunity and the regulation of adaptive immunity. More and more studies revealed the ability of NETs to reshape the tumor immune microenvironmen...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-45558-6 |
| _version_ | 1797630249327919104 |
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| author | Cheng Feng Yuan Li Yi Tai Weili Zhang Hao Wang Shaopu Lian E-er-man-bie-ke Jin-si-han Yuanyuan Liu Xinghui Li Qifeng Chen Meng He Zhenhai Lu |
| author_facet | Cheng Feng Yuan Li Yi Tai Weili Zhang Hao Wang Shaopu Lian E-er-man-bie-ke Jin-si-han Yuanyuan Liu Xinghui Li Qifeng Chen Meng He Zhenhai Lu |
| author_sort | Cheng Feng |
| collection | DOAJ |
| description | Abstract Neutrophil extracellular traps (NETs) have been categorized as a form of inflammatory cell death mode of neutrophils (NETosis) involved in natural immunity and the regulation of adaptive immunity. More and more studies revealed the ability of NETs to reshape the tumor immune microenvironment (TIME) by limiting antitumor effector cells, which may impair the efficacy of immunotherapy. To explore whether NETs-related genes make vital impacts on Colon carcinoma (COAD), we have carried out a systematic analysis and showed several findings in the present work. First, we obtained the patient's data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset, aiming to detect two NETs-associated subtypes by consensus clustering. For the purpose of annotating the roles of NETs-related pathways, gene ontology enrichment analyses were adopted. Next, we constructed a 6 novel NETs-related genes score using the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model. We found that the NETs risk score was notably upregulated in COAD patient samples, and its levels were notably correlated with tumor clinicopathological and immune traits. Then, according to NETs-associated molecular subtypes and the risk signature, this study compared immune cell infiltration calculated through the estimate, CIBERSORT, TIMER, ssGSEA algorithms, tumor immune dysfunction, as well as exclusion (TIDE). Furthermore, we confirm that MPO(myeloperoxidase) was significantly upregulated in COAD patient samples, and its levels were significantly linked to tumor malignancy and clinic outcome. Moreover, multiplex immunohistochemistry (mIHC) spatial analysis confirmed that MPO was closely related to Treg and PD-1 + Treg in spatial location which suggested MPO may paly an important role in TIME formation. Altogether, the obtained results indicated that a six NETs-related genes prognostic signature was conducive to estimating the prognosis and response of chemo-/immuno-therapy of COAD patients. |
| first_indexed | 2024-03-11T11:04:30Z |
| format | Article |
| id | doaj.art-911491888c8c42829d10c1a7af94c5ba |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-11T11:04:30Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-911491888c8c42829d10c1a7af94c5ba2023-11-12T12:17:51ZengNature PortfolioScientific Reports2045-23222023-11-0113111710.1038/s41598-023-45558-6A neutrophil extracellular traps-related classification predicts prognosis and response to immunotherapy in colon cancerCheng Feng0Yuan Li1Yi Tai2Weili Zhang3Hao Wang4Shaopu Lian5E-er-man-bie-ke Jin-si-han6Yuanyuan Liu7Xinghui Li8Qifeng Chen9Meng He10Zhenhai Lu11Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Sun Yat-sen UniversityDepartment of Colorectal Surgery, Sun Yat-sen University Cancer Center, Sun Yat-sen UniversityDepartment of Musculoskeletal Oncology, Sun Yat-Senen University Cancer CenterDepartment of Colorectal Surgery, Sun Yat-sen University Cancer Center, Sun Yat-sen UniversityDepartment of Colorectal Surgery, Sun Yat-sen University Cancer Center, Sun Yat-sen UniversityDepartment of Colorectal Surgery, Sun Yat-sen University Cancer Center, Sun Yat-sen UniversityDepartment of Colorectal Surgery, Sun Yat-sen University Cancer Center, Sun Yat-sen UniversityDepartment of Radiation Oncology, The First Hospital of Hunan University of Chinese MedicineDepartment of Cardiology General Hospital of Xinjiang Military CommandDepartment of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, Sun Yat-Sen University Cancer CenterDepartment of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Colorectal Surgery, Sun Yat-sen University Cancer Center, Sun Yat-sen UniversityAbstract Neutrophil extracellular traps (NETs) have been categorized as a form of inflammatory cell death mode of neutrophils (NETosis) involved in natural immunity and the regulation of adaptive immunity. More and more studies revealed the ability of NETs to reshape the tumor immune microenvironment (TIME) by limiting antitumor effector cells, which may impair the efficacy of immunotherapy. To explore whether NETs-related genes make vital impacts on Colon carcinoma (COAD), we have carried out a systematic analysis and showed several findings in the present work. First, we obtained the patient's data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset, aiming to detect two NETs-associated subtypes by consensus clustering. For the purpose of annotating the roles of NETs-related pathways, gene ontology enrichment analyses were adopted. Next, we constructed a 6 novel NETs-related genes score using the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model. We found that the NETs risk score was notably upregulated in COAD patient samples, and its levels were notably correlated with tumor clinicopathological and immune traits. Then, according to NETs-associated molecular subtypes and the risk signature, this study compared immune cell infiltration calculated through the estimate, CIBERSORT, TIMER, ssGSEA algorithms, tumor immune dysfunction, as well as exclusion (TIDE). Furthermore, we confirm that MPO(myeloperoxidase) was significantly upregulated in COAD patient samples, and its levels were significantly linked to tumor malignancy and clinic outcome. Moreover, multiplex immunohistochemistry (mIHC) spatial analysis confirmed that MPO was closely related to Treg and PD-1 + Treg in spatial location which suggested MPO may paly an important role in TIME formation. Altogether, the obtained results indicated that a six NETs-related genes prognostic signature was conducive to estimating the prognosis and response of chemo-/immuno-therapy of COAD patients.https://doi.org/10.1038/s41598-023-45558-6 |
| spellingShingle | Cheng Feng Yuan Li Yi Tai Weili Zhang Hao Wang Shaopu Lian E-er-man-bie-ke Jin-si-han Yuanyuan Liu Xinghui Li Qifeng Chen Meng He Zhenhai Lu A neutrophil extracellular traps-related classification predicts prognosis and response to immunotherapy in colon cancer Scientific Reports |
| title | A neutrophil extracellular traps-related classification predicts prognosis and response to immunotherapy in colon cancer |
| title_full | A neutrophil extracellular traps-related classification predicts prognosis and response to immunotherapy in colon cancer |
| title_fullStr | A neutrophil extracellular traps-related classification predicts prognosis and response to immunotherapy in colon cancer |
| title_full_unstemmed | A neutrophil extracellular traps-related classification predicts prognosis and response to immunotherapy in colon cancer |
| title_short | A neutrophil extracellular traps-related classification predicts prognosis and response to immunotherapy in colon cancer |
| title_sort | neutrophil extracellular traps related classification predicts prognosis and response to immunotherapy in colon cancer |
| url | https://doi.org/10.1038/s41598-023-45558-6 |
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