Development and functional validation of a disulfidoptosis-related gene prognostic model for lung adenocarcinoma based on bioinformatics and experimental validation
BackgroundDisulfidoptosis is increasingly linked to cancer progression, yet its immunological impacts and prognostic value in lung adenocarcinoma (LUAD) remain poorly understood. This study aims to delineate the predictive significance of disulfidoptosis-related genes (DRGs) in LUAD, their potential...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1540578/full |
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| author | Tao Shen Tao Shen Zhuming Lu Sisi Yang Dongxi Zhang Yongwen Ke Zhuowen Chen Jinqiang Wu Jinqiang Wu Weidong Wu |
| author_facet | Tao Shen Tao Shen Zhuming Lu Sisi Yang Dongxi Zhang Yongwen Ke Zhuowen Chen Jinqiang Wu Jinqiang Wu Weidong Wu |
| author_sort | Tao Shen |
| collection | DOAJ |
| description | BackgroundDisulfidoptosis is increasingly linked to cancer progression, yet its immunological impacts and prognostic value in lung adenocarcinoma (LUAD) remain poorly understood. This study aims to delineate the predictive significance of disulfidoptosis-related genes (DRGs) in LUAD, their potential as therapeutic targets, and their interaction with the tumor microenvironment.MethodsWe analyzed the expression profiles of 23 DRGs and survival data, performing consensus clustering to identify molecular subtypes. Survival analysis and gene set variation analysis (GSVA) were used to explore cluster differences. Key DRGs were selected for Cox and LASSO regression to develop a prognostic model. Tensin4 (TNS4), a key gene in the model, was further evaluated through immunohistochemistry (IHC) in LUAD and normal tissues and gene knockdown experiments in vitro.ResultsTwo clusters were identified, with 225 differentially expressed genes. A six-gene signature was developed, which classified LUAD patients into high- and low-risk groups, showing significant survival differences. The risk score independently predicted LUAD prognosis and correlated with immunotherapy responses. IHC showed elevated TNS4 levels in LUAD tissues, while in vitro TNS4 knockdown reduced both cell proliferation and migration.ConclusionThis study highlights the role of DRGs in LUAD, with a validated gene signature offering new avenues for targeted therapies, potentially improving LUAD treatment outcomes. |
| format | Article |
| id | doaj-art-f1a449fbbc55409b81729263c5cd8d3b |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-f1a449fbbc55409b81729263c5cd8d3b2025-02-10T06:48:33ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15405781540578Development and functional validation of a disulfidoptosis-related gene prognostic model for lung adenocarcinoma based on bioinformatics and experimental validationTao Shen0Tao Shen1Zhuming Lu2Sisi Yang3Dongxi Zhang4Yongwen Ke5Zhuowen Chen6Jinqiang Wu7Jinqiang Wu8Weidong Wu9Department of Surgery, First Clinical Medical College of Jinan University, Guangzhou, Guangdong, ChinaDepartment of Thoracic Surgery, Jiangmen Central Hospital, Jiangmen, Guangdong, ChinaDepartment of Thoracic Surgery, Jiangmen Central Hospital, Jiangmen, Guangdong, ChinaDepartment of Psychology, Jiangmen Third People’s Hospital, Jiangmen, Guangdong, ChinaDepartment of Thoracic Surgery, Jiangmen Central Hospital, Jiangmen, Guangdong, ChinaDepartment of Thoracic Surgery, Jiangmen Central Hospital, Jiangmen, Guangdong, ChinaDepartment of Thoracic Surgery, Jiangmen Central Hospital, Jiangmen, Guangdong, ChinaDepartment of Cardiothoracic Vascular Surgery, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, ChinaBaise Key Laboratory of Molecular Pathology in Tumors, Baise, Guangxi, ChinaDepartment of Cardiothoracic Vascular Surgery, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, Guangdong, ChinaBackgroundDisulfidoptosis is increasingly linked to cancer progression, yet its immunological impacts and prognostic value in lung adenocarcinoma (LUAD) remain poorly understood. This study aims to delineate the predictive significance of disulfidoptosis-related genes (DRGs) in LUAD, their potential as therapeutic targets, and their interaction with the tumor microenvironment.MethodsWe analyzed the expression profiles of 23 DRGs and survival data, performing consensus clustering to identify molecular subtypes. Survival analysis and gene set variation analysis (GSVA) were used to explore cluster differences. Key DRGs were selected for Cox and LASSO regression to develop a prognostic model. Tensin4 (TNS4), a key gene in the model, was further evaluated through immunohistochemistry (IHC) in LUAD and normal tissues and gene knockdown experiments in vitro.ResultsTwo clusters were identified, with 225 differentially expressed genes. A six-gene signature was developed, which classified LUAD patients into high- and low-risk groups, showing significant survival differences. The risk score independently predicted LUAD prognosis and correlated with immunotherapy responses. IHC showed elevated TNS4 levels in LUAD tissues, while in vitro TNS4 knockdown reduced both cell proliferation and migration.ConclusionThis study highlights the role of DRGs in LUAD, with a validated gene signature offering new avenues for targeted therapies, potentially improving LUAD treatment outcomes.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1540578/fullLUADdisulfidptosistumor microenvironmentsprognosisimmunotherapy |
| spellingShingle | Tao Shen Tao Shen Zhuming Lu Sisi Yang Dongxi Zhang Yongwen Ke Zhuowen Chen Jinqiang Wu Jinqiang Wu Weidong Wu Development and functional validation of a disulfidoptosis-related gene prognostic model for lung adenocarcinoma based on bioinformatics and experimental validation Frontiers in Immunology LUAD disulfidptosis tumor microenvironments prognosis immunotherapy |
| title | Development and functional validation of a disulfidoptosis-related gene prognostic model for lung adenocarcinoma based on bioinformatics and experimental validation |
| title_full | Development and functional validation of a disulfidoptosis-related gene prognostic model for lung adenocarcinoma based on bioinformatics and experimental validation |
| title_fullStr | Development and functional validation of a disulfidoptosis-related gene prognostic model for lung adenocarcinoma based on bioinformatics and experimental validation |
| title_full_unstemmed | Development and functional validation of a disulfidoptosis-related gene prognostic model for lung adenocarcinoma based on bioinformatics and experimental validation |
| title_short | Development and functional validation of a disulfidoptosis-related gene prognostic model for lung adenocarcinoma based on bioinformatics and experimental validation |
| title_sort | development and functional validation of a disulfidoptosis related gene prognostic model for lung adenocarcinoma based on bioinformatics and experimental validation |
| topic | LUAD disulfidptosis tumor microenvironments prognosis immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1540578/full |
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