Development and validation of a disulfidptosis-related genes signature for predicting outcomes and immunotherapy in acute myeloid leukemia
BackgroundAcute myeloid leukemia (AML) is a hematopoietic malignancy with poor outcomes and high recurrence. Disulfidptosis, a novel form of programmed cell death driven by aberrant disulfide bonds and F-actin collapse, provides insights into cancer progression and treatment.MethodsWe investigated t...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1513040/full |
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| author | Han Gong Han Gong Ying Zhang Xusheng Wu Yiming Pan Yiming Pan Mingwei Wang Mingwei Wang Xiaofeng He Jing Liu Zhong Liu Zhong Liu Ling Li |
| author_facet | Han Gong Han Gong Ying Zhang Xusheng Wu Yiming Pan Yiming Pan Mingwei Wang Mingwei Wang Xiaofeng He Jing Liu Zhong Liu Zhong Liu Ling Li |
| author_sort | Han Gong |
| collection | DOAJ |
| description | BackgroundAcute myeloid leukemia (AML) is a hematopoietic malignancy with poor outcomes and high recurrence. Disulfidptosis, a novel form of programmed cell death driven by aberrant disulfide bonds and F-actin collapse, provides insights into cancer progression and treatment.MethodsWe investigated the correlation network and prognostic values of disulfidptosis-related genes (DRGs) in AML. Unsupervised clustering was performed to reveal distinct disulfidptosis-related AML subtypes. We implemented the differential analysis and enrichment analysis to explore the difference of the distinct subtypes in biological processes. Least absolute shrinkage and selection operator (LASSO) Cox model was used to generate a disulfidptosis-related signature. We employed the ESTIMATE, CIBERSORT, and scRNA analyses to assess the tumor microenvironment of AML. Moreover, experiments validated the functions of PTPN6 and CSK in OCI-AML2 cells.ResultsWe identified 10 prognostic DRGs and revealed two disulfidptosis subtypes. DRGs significantly affected immune processes like interferon-gamma response and MHC class II antigen presentation. LASSO algorithm was implemented to established a 6-gene signature (HLA-DRB5, CCDC124, PTPN6, HLA-DMA, CSK, ISG15) that predicted prognosis in two validation cohorts more robustly than other signatures. Disulfidptosis was correlated with tumor microenvironment immune cells, especially monocytes. The two risk subgroups differed significantly in susceptibilities of multiple chemotherapy drugs, indicating disulfidptosis as a potential therapeutic target. Knockdown of PTPN6 and CSK inhibited the proliferation of AML cells and increased apoptosis.ConclusionsOur study provides insights into DRG prognoses and immunomodulation, establishing a robust 6-gene risk model for predicting AML outcomes that may enhance precision medicine and treatment strategies. |
| format | Article |
| id | doaj-art-ed8e61eee112437a92665bd61a69bde2 |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-ed8e61eee112437a92665bd61a69bde22025-08-20T03:05:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.15130401513040Development and validation of a disulfidptosis-related genes signature for predicting outcomes and immunotherapy in acute myeloid leukemiaHan Gong0Han Gong1Ying Zhang2Xusheng Wu3Yiming Pan4Yiming Pan5Mingwei Wang6Mingwei Wang7Xiaofeng He8Jing Liu9Zhong Liu10Zhong Liu11Ling Li12Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, ChinaDepartment of Hematology, The Second Xiangya Hospital, Molecular Biology Research Center, School of Life Sciences, Hunan Province Key Laboratory of Basic and Applied Hematology, Central South University, Changsha, ChinaThe Institute of Medical Information (IMI) & Library, Chinese Academy of Medical Sciences and Peking Union Medical, Beijing, ChinaShenzhen Health Development Research and Data Management Center, Shenzhen, ChinaInstitute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, ChinaKey laboratory of transfusion adverse reactions, Chinese Academy of Medical Sciences, Chengdu, ChinaInstitute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, ChinaKey laboratory of transfusion adverse reactions, Chinese Academy of Medical Sciences, Chengdu, ChinaShenzhen Health Development Research and Data Management Center, Shenzhen, ChinaDepartment of Hematology, The Second Xiangya Hospital, Molecular Biology Research Center, School of Life Sciences, Hunan Province Key Laboratory of Basic and Applied Hematology, Central South University, Changsha, ChinaInstitute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, ChinaKey laboratory of transfusion adverse reactions, Chinese Academy of Medical Sciences, Chengdu, ChinaDepartment of Blood Transfusion, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, Sichuan, ChinaBackgroundAcute myeloid leukemia (AML) is a hematopoietic malignancy with poor outcomes and high recurrence. Disulfidptosis, a novel form of programmed cell death driven by aberrant disulfide bonds and F-actin collapse, provides insights into cancer progression and treatment.MethodsWe investigated the correlation network and prognostic values of disulfidptosis-related genes (DRGs) in AML. Unsupervised clustering was performed to reveal distinct disulfidptosis-related AML subtypes. We implemented the differential analysis and enrichment analysis to explore the difference of the distinct subtypes in biological processes. Least absolute shrinkage and selection operator (LASSO) Cox model was used to generate a disulfidptosis-related signature. We employed the ESTIMATE, CIBERSORT, and scRNA analyses to assess the tumor microenvironment of AML. Moreover, experiments validated the functions of PTPN6 and CSK in OCI-AML2 cells.ResultsWe identified 10 prognostic DRGs and revealed two disulfidptosis subtypes. DRGs significantly affected immune processes like interferon-gamma response and MHC class II antigen presentation. LASSO algorithm was implemented to established a 6-gene signature (HLA-DRB5, CCDC124, PTPN6, HLA-DMA, CSK, ISG15) that predicted prognosis in two validation cohorts more robustly than other signatures. Disulfidptosis was correlated with tumor microenvironment immune cells, especially monocytes. The two risk subgroups differed significantly in susceptibilities of multiple chemotherapy drugs, indicating disulfidptosis as a potential therapeutic target. Knockdown of PTPN6 and CSK inhibited the proliferation of AML cells and increased apoptosis.ConclusionsOur study provides insights into DRG prognoses and immunomodulation, establishing a robust 6-gene risk model for predicting AML outcomes that may enhance precision medicine and treatment strategies.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1513040/fullacute myeloid leukemiadisulfidptosis-related genesprognosisrisk modelimmunomodulationtumor microenvironment |
| spellingShingle | Han Gong Han Gong Ying Zhang Xusheng Wu Yiming Pan Yiming Pan Mingwei Wang Mingwei Wang Xiaofeng He Jing Liu Zhong Liu Zhong Liu Ling Li Development and validation of a disulfidptosis-related genes signature for predicting outcomes and immunotherapy in acute myeloid leukemia Frontiers in Immunology acute myeloid leukemia disulfidptosis-related genes prognosis risk model immunomodulation tumor microenvironment |
| title | Development and validation of a disulfidptosis-related genes signature for predicting outcomes and immunotherapy in acute myeloid leukemia |
| title_full | Development and validation of a disulfidptosis-related genes signature for predicting outcomes and immunotherapy in acute myeloid leukemia |
| title_fullStr | Development and validation of a disulfidptosis-related genes signature for predicting outcomes and immunotherapy in acute myeloid leukemia |
| title_full_unstemmed | Development and validation of a disulfidptosis-related genes signature for predicting outcomes and immunotherapy in acute myeloid leukemia |
| title_short | Development and validation of a disulfidptosis-related genes signature for predicting outcomes and immunotherapy in acute myeloid leukemia |
| title_sort | development and validation of a disulfidptosis related genes signature for predicting outcomes and immunotherapy in acute myeloid leukemia |
| topic | acute myeloid leukemia disulfidptosis-related genes prognosis risk model immunomodulation tumor microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1513040/full |
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