A novel classification method for LUAD that guides personalized immunotherapy on the basis of the cross-talk of coagulation- and macrophage-related genes
PurposeThe coagulation process and infiltration of macrophages affect the progression and prognosis of lung adenocarcinoma (LUAD) patients. This study was designed to explore novel classification methods that better guide the precise treatment of LUAD patients on the basis of coagulation and macroph...
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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.2025.1518102/full |
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| author | Zhuoqi Li Ling Chen Zhigang Wei Hongtao Liu Lu Zhang Fujing Huang Xiao Wen Yuan Tian |
| author_facet | Zhuoqi Li Ling Chen Zhigang Wei Hongtao Liu Lu Zhang Fujing Huang Xiao Wen Yuan Tian |
| author_sort | Zhuoqi Li |
| collection | DOAJ |
| description | PurposeThe coagulation process and infiltration of macrophages affect the progression and prognosis of lung adenocarcinoma (LUAD) patients. This study was designed to explore novel classification methods that better guide the precise treatment of LUAD patients on the basis of coagulation and macrophages.MethodsWeighted gene coexpression network analysis (WGCNA) was applied to identify M2 macrophage-related genes, and TAM marker genes were acquired through the analysis of scRNA-seq data. The MSigDB and KEGG databases were used to obtain coagulation-associated genes. The intersecting genes were defined as coagulation and macrophage-related (COMAR) genes. Unsupervised clustering analysis was used to evaluate distinct COMAR patterns for LUAD patients on the basis of the COMAR genes. The R package “limma” was used to identify differentially expressed genes (DEGs) between COMAR patterns. A prognostic risk score model, which was validated through external data cohorts and clinical samples, was constructed on the basis of the COMAR DEGs.ResultsIn total, 33 COMAR genes were obtained, and three COMAR LUAD subtypes were identified on the basis of the 33 COMAR genes. There were 341 DEGs identified between the three COMAR subtypes, and 60 prognostic genes were selected for constructing the COMAR risk score model. Finally, 15 prognosis-associated genes (CORO1A, EPHA4, FOXM1, HLF, IFIH1, KYNU, LY6D, MUC16, PPARG, S100A8, SPINK1, SPINK5, SPP1, VSIG4, and XIST) were included in the model, which was efficient and robust in predicting LUAD patient prognosis and clinical outcomes in patients receiving anti-PD-1/PD-L1 immunotherapy.ConclusionsLUAD can be classified into three subtypes according to COMAR genes, which may provide guidance for precise treatment. |
| format | Article |
| id | doaj-art-215e0fcd22cd42dbaa3d155dca71aeee |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-215e0fcd22cd42dbaa3d155dca71aeee2025-08-20T02:13:39ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15181021518102A novel classification method for LUAD that guides personalized immunotherapy on the basis of the cross-talk of coagulation- and macrophage-related genesZhuoqi Li0Ling Chen1Zhigang Wei2Hongtao Liu3Lu Zhang4Fujing Huang5Xiao Wen6Yuan Tian7Department of Radiotherapy Oncology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, ChinaDepartment of Oncology, Qingdao Municipal Hospital, Qingdao, ChinaDepartment of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Lung Cancer Institute, Jinan, ChinaDepartment of Pathology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Clinical Pathology, Shandong Lung Cancer Institute, Shandong Institute of Nephrology, Jinan, ChinaDepartment of Radiotherapy Oncology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, ChinaDepartment of Radiotherapy Oncology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, ChinaDepartment of Radiotherapy Oncology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, ChinaDepartment of Radiotherapy Oncology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, ChinaPurposeThe coagulation process and infiltration of macrophages affect the progression and prognosis of lung adenocarcinoma (LUAD) patients. This study was designed to explore novel classification methods that better guide the precise treatment of LUAD patients on the basis of coagulation and macrophages.MethodsWeighted gene coexpression network analysis (WGCNA) was applied to identify M2 macrophage-related genes, and TAM marker genes were acquired through the analysis of scRNA-seq data. The MSigDB and KEGG databases were used to obtain coagulation-associated genes. The intersecting genes were defined as coagulation and macrophage-related (COMAR) genes. Unsupervised clustering analysis was used to evaluate distinct COMAR patterns for LUAD patients on the basis of the COMAR genes. The R package “limma” was used to identify differentially expressed genes (DEGs) between COMAR patterns. A prognostic risk score model, which was validated through external data cohorts and clinical samples, was constructed on the basis of the COMAR DEGs.ResultsIn total, 33 COMAR genes were obtained, and three COMAR LUAD subtypes were identified on the basis of the 33 COMAR genes. There were 341 DEGs identified between the three COMAR subtypes, and 60 prognostic genes were selected for constructing the COMAR risk score model. Finally, 15 prognosis-associated genes (CORO1A, EPHA4, FOXM1, HLF, IFIH1, KYNU, LY6D, MUC16, PPARG, S100A8, SPINK1, SPINK5, SPP1, VSIG4, and XIST) were included in the model, which was efficient and robust in predicting LUAD patient prognosis and clinical outcomes in patients receiving anti-PD-1/PD-L1 immunotherapy.ConclusionsLUAD can be classified into three subtypes according to COMAR genes, which may provide guidance for precise treatment.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1518102/fullcoagulationmacrophageprognosisLUADclassification methodsrisk score model |
| spellingShingle | Zhuoqi Li Ling Chen Zhigang Wei Hongtao Liu Lu Zhang Fujing Huang Xiao Wen Yuan Tian A novel classification method for LUAD that guides personalized immunotherapy on the basis of the cross-talk of coagulation- and macrophage-related genes Frontiers in Immunology coagulation macrophage prognosis LUAD classification methods risk score model |
| title | A novel classification method for LUAD that guides personalized immunotherapy on the basis of the cross-talk of coagulation- and macrophage-related genes |
| title_full | A novel classification method for LUAD that guides personalized immunotherapy on the basis of the cross-talk of coagulation- and macrophage-related genes |
| title_fullStr | A novel classification method for LUAD that guides personalized immunotherapy on the basis of the cross-talk of coagulation- and macrophage-related genes |
| title_full_unstemmed | A novel classification method for LUAD that guides personalized immunotherapy on the basis of the cross-talk of coagulation- and macrophage-related genes |
| title_short | A novel classification method for LUAD that guides personalized immunotherapy on the basis of the cross-talk of coagulation- and macrophage-related genes |
| title_sort | novel classification method for luad that guides personalized immunotherapy on the basis of the cross talk of coagulation and macrophage related genes |
| topic | coagulation macrophage prognosis LUAD classification methods risk score model |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1518102/full |
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