Disulfidptosis-related gene signatures as prognostic biomarkers and predictors of immunotherapy response in HNSCC
BackgroundDisulfidptosis is a newly discovered form of cell death associated with tumorigenesis, particularly under oxidative stress and metabolic disorder conditions. Currently, the biological mechanisms of disulfidptosis-related genes (DRGs) in head and neck squamous cell carcinoma (HNSCC) remain...
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Frontiers Media S.A.
2025-01-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1456649/full |
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| author | Haotian Qin Haotian Qin Juan Xu Yaohang Yue Yaohang Yue Meiling Chen Zheng Zhang Panpan Xu Yan Zheng Hui Zeng Jian Weng Jian Weng Jun Yang Fei Yu |
| author_facet | Haotian Qin Haotian Qin Juan Xu Yaohang Yue Yaohang Yue Meiling Chen Zheng Zhang Panpan Xu Yan Zheng Hui Zeng Jian Weng Jian Weng Jun Yang Fei Yu |
| author_sort | Haotian Qin |
| collection | DOAJ |
| description | BackgroundDisulfidptosis is a newly discovered form of cell death associated with tumorigenesis, particularly under oxidative stress and metabolic disorder conditions. Currently, the biological mechanisms of disulfidptosis-related genes (DRGs) in head and neck squamous cell carcinoma (HNSCC) remain unclear.MethodsThe study includes sections on methodologies, data sources, clinical data collection, subtype establishment, identification and analysis of differentially expressed genes, genetic variation, and the construction and validation of a DRG prognostic model. Various analyses are conducted, including the relationship between the risk scores model and clinicopathological features, immune status, immune checkpoints, tumor mutational burden (TMB), microsatellite instability (MSI), ESTIMATE, mRNAsi, and drug sensitivity. The study also covers single-cell analysis and DNA methylation analysis of DRGs, and the prediction of potential microRNA and long non-coding RNA target genes. Prognostic DRGs expression in HNSCC is validated through RT-qPCR and immunohistochemistry. The model’s predictive capability is confirmed using external validation cohorts from GEO datasets and clinical tissue samples. The role of DSTN in HNSCC is further validated through gene knockout experiments.ResultsWe identified four valuable genes (SLC3A2, NUBPL, ACTB, DSTN) and constructed a prognostic model, along with identifying two DRG-related subtypes. Analysis of the DRG risk score revealed that the low-risk group had a better prognosis compared to the high-risk group. Significant correlations were found between the DRG risk score and clinical features, immunotherapy response, drug sensitivity, and genes related to RNA epigenetic modifications. Low-risk HNSCC patients were identified as potential beneficiaries of immune checkpoint inhibitor (ICI) therapy. A regulatory axis involving DSTN, hsa-miR-181c-5p, LUCAT1, and IGFL2-AS1 was constructed for HNSCC. RT-qPCR and IHC data further validated the upregulation of prognostic DRGs in HNSCC. The prognostic model demonstrated excellent predictive performance for the prognosis of HNSCC patients. Additionally, DSTN was significantly overexpressed in tumor cells; its knockdown inhibited tumor cell proliferation, migration, and invasion.ConclusionThe prognostic model effectively predicts HNSCC outcomes, with better prognosis in the low-risk group. DSTN upregulation promotes tumor growth, and its knockout inhibits proliferation, migration, and invasion. |
| format | Article |
| id | doaj-art-6efa566ec59e4bae84af926ab4adee80 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-6efa566ec59e4bae84af926ab4adee802025-01-17T06:51:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.14566491456649Disulfidptosis-related gene signatures as prognostic biomarkers and predictors of immunotherapy response in HNSCCHaotian Qin0Haotian Qin1Juan Xu2Yaohang Yue3Yaohang Yue4Meiling Chen5Zheng Zhang6Panpan Xu7Yan Zheng8Hui Zeng9Jian Weng10Jian Weng11Jun Yang12Fei Yu13Department of Bone and Joint Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong, ChinaShenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, Peking University Shenzhen Hospital, Shenzhen, Guangdong, ChinaDepartment of Oncology, Chaohu Hospital of Anhui Medical University, Hefei, ChinaDepartment of Bone and Joint Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong, ChinaShenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, Peking University Shenzhen Hospital, Shenzhen, Guangdong, ChinaOperating Room, Peking University Shenzhen Hospital, Shenzhen, ChinaStomatological Center, Peking University Shenzhen Hospital, Shenzhen, ChinaDepartment of Otolaryngology Head and Neck Surgery, Chaohu Hospital of Anhui Medical University, Hefei, ChinaDepartment of Pathology, Chaohu Hospital of Anhui Medical University, Hefei, ChinaDepartment of Orthopedics, Medical Innovation Technology Transformation Center of Shenzhen Second People’s Hospital, Shenzhen Second People’s Hospital, Shenzhen, Guangdong, ChinaDepartment of Bone and Joint Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong, ChinaShenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, Peking University Shenzhen Hospital, Shenzhen, Guangdong, ChinaDepartment of Radiology, Peking University Shenzhen Hospital, Shenzhen, China0Department of Spine Surgery, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, ChinaBackgroundDisulfidptosis is a newly discovered form of cell death associated with tumorigenesis, particularly under oxidative stress and metabolic disorder conditions. Currently, the biological mechanisms of disulfidptosis-related genes (DRGs) in head and neck squamous cell carcinoma (HNSCC) remain unclear.MethodsThe study includes sections on methodologies, data sources, clinical data collection, subtype establishment, identification and analysis of differentially expressed genes, genetic variation, and the construction and validation of a DRG prognostic model. Various analyses are conducted, including the relationship between the risk scores model and clinicopathological features, immune status, immune checkpoints, tumor mutational burden (TMB), microsatellite instability (MSI), ESTIMATE, mRNAsi, and drug sensitivity. The study also covers single-cell analysis and DNA methylation analysis of DRGs, and the prediction of potential microRNA and long non-coding RNA target genes. Prognostic DRGs expression in HNSCC is validated through RT-qPCR and immunohistochemistry. The model’s predictive capability is confirmed using external validation cohorts from GEO datasets and clinical tissue samples. The role of DSTN in HNSCC is further validated through gene knockout experiments.ResultsWe identified four valuable genes (SLC3A2, NUBPL, ACTB, DSTN) and constructed a prognostic model, along with identifying two DRG-related subtypes. Analysis of the DRG risk score revealed that the low-risk group had a better prognosis compared to the high-risk group. Significant correlations were found between the DRG risk score and clinical features, immunotherapy response, drug sensitivity, and genes related to RNA epigenetic modifications. Low-risk HNSCC patients were identified as potential beneficiaries of immune checkpoint inhibitor (ICI) therapy. A regulatory axis involving DSTN, hsa-miR-181c-5p, LUCAT1, and IGFL2-AS1 was constructed for HNSCC. RT-qPCR and IHC data further validated the upregulation of prognostic DRGs in HNSCC. The prognostic model demonstrated excellent predictive performance for the prognosis of HNSCC patients. Additionally, DSTN was significantly overexpressed in tumor cells; its knockdown inhibited tumor cell proliferation, migration, and invasion.ConclusionThe prognostic model effectively predicts HNSCC outcomes, with better prognosis in the low-risk group. DSTN upregulation promotes tumor growth, and its knockout inhibits proliferation, migration, and invasion.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1456649/fulldisulfidptosishead and neck squamous cell carcinomaprognostic signaturesbioinformatics analysisimmunotherapy response |
| spellingShingle | Haotian Qin Haotian Qin Juan Xu Yaohang Yue Yaohang Yue Meiling Chen Zheng Zhang Panpan Xu Yan Zheng Hui Zeng Jian Weng Jian Weng Jun Yang Fei Yu Disulfidptosis-related gene signatures as prognostic biomarkers and predictors of immunotherapy response in HNSCC Frontiers in Immunology disulfidptosis head and neck squamous cell carcinoma prognostic signatures bioinformatics analysis immunotherapy response |
| title | Disulfidptosis-related gene signatures as prognostic biomarkers and predictors of immunotherapy response in HNSCC |
| title_full | Disulfidptosis-related gene signatures as prognostic biomarkers and predictors of immunotherapy response in HNSCC |
| title_fullStr | Disulfidptosis-related gene signatures as prognostic biomarkers and predictors of immunotherapy response in HNSCC |
| title_full_unstemmed | Disulfidptosis-related gene signatures as prognostic biomarkers and predictors of immunotherapy response in HNSCC |
| title_short | Disulfidptosis-related gene signatures as prognostic biomarkers and predictors of immunotherapy response in HNSCC |
| title_sort | disulfidptosis related gene signatures as prognostic biomarkers and predictors of immunotherapy response in hnscc |
| topic | disulfidptosis head and neck squamous cell carcinoma prognostic signatures bioinformatics analysis immunotherapy response |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1456649/full |
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