The causal relationship between circulating inflammatory proteins, gut microbiotas, immune cells and leukemia: a bidirectional Mendelian randomization study
Abstract Introduction Numerous evidence have highlighted a robust association between inflammatory proteins, gut microbiotas, and immune cells and leukemia. However, the causal relationship remains poorly defined. To delve into this connection, we implemented a bidirectional Mendelian randomization...
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| Format: | Article |
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Springer
2025-06-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-02863-y |
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| author | Linying Zhu Xiaoyi Ruan Yilun Zou Shuikang Ye Liangzhen Xie |
| author_facet | Linying Zhu Xiaoyi Ruan Yilun Zou Shuikang Ye Liangzhen Xie |
| author_sort | Linying Zhu |
| collection | DOAJ |
| description | Abstract Introduction Numerous evidence have highlighted a robust association between inflammatory proteins, gut microbiotas, and immune cells and leukemia. However, the causal relationship remains poorly defined. To delve into this connection, we implemented a bidirectional Mendelian randomization (MR) study. Materials and methods This study utilized genetic variation data from publicly accessible genome-wide association study (GWAS) datasets. We used methods such as inverse variance weighting (IVW) to assess the causal relationship between exposure and the outcome of leukemia. Mediation analyses were applied to investigate the associations between immunophenotypes, gut microbiotas and inflammatory proteins and leukemia. Instrumental variables (IVs) mapping genes were identified, and functional analyses of the related genes were subsequently carried out. Sensitivity analyses was implemented to fortify the robustness of methods and results. Results This study uncovered four inflammatory proteins exhibiting significant associations with elevated leukemia risk, while leukemia exerted discernible effects on six inflammatory cytokines. IVW analysis revealed two immune cell subtypes with opposing roles on leukemia risk. One gut microbiota subtypes exhibited a pro-leukemogenic association, contrasted by four subtypes displaying protective influences. Enrichment analysis further identified three differentially expressed genes between malignant and adjacent normal tissues, with related genes demonstrated pronounced pathway enrichment in the mitogen-activated protein kinase (MAPK) signaling pathway. Conclusion These findings shed new light on the genetic associations between circulating inflammatory proteins, gut microbiotas, and immune cells and leukemia. It may not only enrich the understanding but also guide deeper clinical and basic research in this domain. |
| format | Article |
| id | doaj-art-6d03dd17c27445df80761d804bff14ea |
| institution | DOAJ |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-6d03dd17c27445df80761d804bff14ea2025-08-20T03:22:50ZengSpringerDiscover Oncology2730-60112025-06-0116111410.1007/s12672-025-02863-yThe causal relationship between circulating inflammatory proteins, gut microbiotas, immune cells and leukemia: a bidirectional Mendelian randomization studyLinying Zhu0Xiaoyi Ruan1Yilun Zou2Shuikang Ye3Liangzhen Xie4School of Obstetrics and Pediatrics, Guangdong Medical UniversityThe First Clinical College, Guangdong Medical UniversitySchool of Clinical Medicine, Shandong Second Medical UniversitySchool of Obstetrics and Pediatrics, Guangdong Medical UniversityGeriatric Department, Nanfang Hospital of Southern Medical UniversityAbstract Introduction Numerous evidence have highlighted a robust association between inflammatory proteins, gut microbiotas, and immune cells and leukemia. However, the causal relationship remains poorly defined. To delve into this connection, we implemented a bidirectional Mendelian randomization (MR) study. Materials and methods This study utilized genetic variation data from publicly accessible genome-wide association study (GWAS) datasets. We used methods such as inverse variance weighting (IVW) to assess the causal relationship between exposure and the outcome of leukemia. Mediation analyses were applied to investigate the associations between immunophenotypes, gut microbiotas and inflammatory proteins and leukemia. Instrumental variables (IVs) mapping genes were identified, and functional analyses of the related genes were subsequently carried out. Sensitivity analyses was implemented to fortify the robustness of methods and results. Results This study uncovered four inflammatory proteins exhibiting significant associations with elevated leukemia risk, while leukemia exerted discernible effects on six inflammatory cytokines. IVW analysis revealed two immune cell subtypes with opposing roles on leukemia risk. One gut microbiota subtypes exhibited a pro-leukemogenic association, contrasted by four subtypes displaying protective influences. Enrichment analysis further identified three differentially expressed genes between malignant and adjacent normal tissues, with related genes demonstrated pronounced pathway enrichment in the mitogen-activated protein kinase (MAPK) signaling pathway. Conclusion These findings shed new light on the genetic associations between circulating inflammatory proteins, gut microbiotas, and immune cells and leukemia. It may not only enrich the understanding but also guide deeper clinical and basic research in this domain.https://doi.org/10.1007/s12672-025-02863-yLeukemiaCirculating inflammatory proteinsMendelian randomizationCausal relationshipGenome-wide association study |
| spellingShingle | Linying Zhu Xiaoyi Ruan Yilun Zou Shuikang Ye Liangzhen Xie The causal relationship between circulating inflammatory proteins, gut microbiotas, immune cells and leukemia: a bidirectional Mendelian randomization study Discover Oncology Leukemia Circulating inflammatory proteins Mendelian randomization Causal relationship Genome-wide association study |
| title | The causal relationship between circulating inflammatory proteins, gut microbiotas, immune cells and leukemia: a bidirectional Mendelian randomization study |
| title_full | The causal relationship between circulating inflammatory proteins, gut microbiotas, immune cells and leukemia: a bidirectional Mendelian randomization study |
| title_fullStr | The causal relationship between circulating inflammatory proteins, gut microbiotas, immune cells and leukemia: a bidirectional Mendelian randomization study |
| title_full_unstemmed | The causal relationship between circulating inflammatory proteins, gut microbiotas, immune cells and leukemia: a bidirectional Mendelian randomization study |
| title_short | The causal relationship between circulating inflammatory proteins, gut microbiotas, immune cells and leukemia: a bidirectional Mendelian randomization study |
| title_sort | causal relationship between circulating inflammatory proteins gut microbiotas immune cells and leukemia a bidirectional mendelian randomization study |
| topic | Leukemia Circulating inflammatory proteins Mendelian randomization Causal relationship Genome-wide association study |
| url | https://doi.org/10.1007/s12672-025-02863-y |
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