The role of immune cells phenotype in neuroendocrine tumors development
Abstract Background Neuroendocrine tumors (NETs) are closely linked to immune disorders, yet the causal relationship between them remains incompletely explored. This study investigates the causal associations between 731 immune features and six types of NETs. Method A bidirectional, two-sample Mende...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer
2025-06-01
|
| Series: | Discover Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s12672-025-02870-z |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849725169412603904 |
|---|---|
| author | Jie Qiao Yi-Wen Wu Yuan-You Wang Jing-Jing Huang Peng-Fei Shan |
| author_facet | Jie Qiao Yi-Wen Wu Yuan-You Wang Jing-Jing Huang Peng-Fei Shan |
| author_sort | Jie Qiao |
| collection | DOAJ |
| description | Abstract Background Neuroendocrine tumors (NETs) are closely linked to immune disorders, yet the causal relationship between them remains incompletely explored. This study investigates the causal associations between 731 immune features and six types of NETs. Method A bidirectional, two-sample Mendelian randomization (MR) analysis is employed to examine the causal relationship between immune cell characteristics and NETs. Publicly available genome-wide association study (GWAS) genetic data are analyzed to explore causal links between 731 immune cell phenotypes and the risk of six NETs. Results After false discovery rate (FDR) correction, no statistically significant effect of the six NETs on the immunophenotype is observed. However, T cells play a crucial role in the development of gastric neuroendocrine tumors (GNETs). Specifically, SSC-A on CD4+ T cells significantly reduces the likelihood of developing GNETs, with an odds ratio (OR) of 0.16 (95% CI=0.084-0.328, P = 2.58×10⁻⁷, FDR = 1.16×10⁻⁴). Terminally differentiated CD4⁻CD8⁻ T cells (OR=14.37, 95% CI=3.647-56.587, P =1.39×10⁻⁴, FDR=0.021) and naive CD4+ T cells (OR=5.32, 95% CI=2.513-11.284, P =1.27×10⁻⁵, FDR=0.0029) are associated with an increased risk of GNETs. Conclusions This study elucidates the causal relationship between 731 immune cells and six types of NETs, identifying three immune phenotypes significantly associated with GNETs pathogenesis. These findings provide new perspectives for future medical research. |
| format | Article |
| id | doaj-art-feef6d28b5054fd183a9fa9364aba081 |
| institution | DOAJ |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-feef6d28b5054fd183a9fa9364aba0812025-08-20T03:10:32ZengSpringerDiscover Oncology2730-60112025-06-011611910.1007/s12672-025-02870-zThe role of immune cells phenotype in neuroendocrine tumors developmentJie Qiao0Yi-Wen Wu1Yuan-You Wang2Jing-Jing Huang3Peng-Fei Shan4Department of Endocrinology and Metabolism, The Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Neurosurgery, The Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Endocrinology and Metabolism, The Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Endocrinology and Metabolism, The Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Endocrinology and Metabolism, The Second Affiliated Hospital, Zhejiang University School of MedicineAbstract Background Neuroendocrine tumors (NETs) are closely linked to immune disorders, yet the causal relationship between them remains incompletely explored. This study investigates the causal associations between 731 immune features and six types of NETs. Method A bidirectional, two-sample Mendelian randomization (MR) analysis is employed to examine the causal relationship between immune cell characteristics and NETs. Publicly available genome-wide association study (GWAS) genetic data are analyzed to explore causal links between 731 immune cell phenotypes and the risk of six NETs. Results After false discovery rate (FDR) correction, no statistically significant effect of the six NETs on the immunophenotype is observed. However, T cells play a crucial role in the development of gastric neuroendocrine tumors (GNETs). Specifically, SSC-A on CD4+ T cells significantly reduces the likelihood of developing GNETs, with an odds ratio (OR) of 0.16 (95% CI=0.084-0.328, P = 2.58×10⁻⁷, FDR = 1.16×10⁻⁴). Terminally differentiated CD4⁻CD8⁻ T cells (OR=14.37, 95% CI=3.647-56.587, P =1.39×10⁻⁴, FDR=0.021) and naive CD4+ T cells (OR=5.32, 95% CI=2.513-11.284, P =1.27×10⁻⁵, FDR=0.0029) are associated with an increased risk of GNETs. Conclusions This study elucidates the causal relationship between 731 immune cells and six types of NETs, identifying three immune phenotypes significantly associated with GNETs pathogenesis. These findings provide new perspectives for future medical research.https://doi.org/10.1007/s12672-025-02870-zNeuroendocrine tumorsImmunophenotypesCausal relationshipMR analysisSensitivity |
| spellingShingle | Jie Qiao Yi-Wen Wu Yuan-You Wang Jing-Jing Huang Peng-Fei Shan The role of immune cells phenotype in neuroendocrine tumors development Discover Oncology Neuroendocrine tumors Immunophenotypes Causal relationship MR analysis Sensitivity |
| title | The role of immune cells phenotype in neuroendocrine tumors development |
| title_full | The role of immune cells phenotype in neuroendocrine tumors development |
| title_fullStr | The role of immune cells phenotype in neuroendocrine tumors development |
| title_full_unstemmed | The role of immune cells phenotype in neuroendocrine tumors development |
| title_short | The role of immune cells phenotype in neuroendocrine tumors development |
| title_sort | role of immune cells phenotype in neuroendocrine tumors development |
| topic | Neuroendocrine tumors Immunophenotypes Causal relationship MR analysis Sensitivity |
| url | https://doi.org/10.1007/s12672-025-02870-z |
| work_keys_str_mv | AT jieqiao theroleofimmunecellsphenotypeinneuroendocrinetumorsdevelopment AT yiwenwu theroleofimmunecellsphenotypeinneuroendocrinetumorsdevelopment AT yuanyouwang theroleofimmunecellsphenotypeinneuroendocrinetumorsdevelopment AT jingjinghuang theroleofimmunecellsphenotypeinneuroendocrinetumorsdevelopment AT pengfeishan theroleofimmunecellsphenotypeinneuroendocrinetumorsdevelopment AT jieqiao roleofimmunecellsphenotypeinneuroendocrinetumorsdevelopment AT yiwenwu roleofimmunecellsphenotypeinneuroendocrinetumorsdevelopment AT yuanyouwang roleofimmunecellsphenotypeinneuroendocrinetumorsdevelopment AT jingjinghuang roleofimmunecellsphenotypeinneuroendocrinetumorsdevelopment AT pengfeishan roleofimmunecellsphenotypeinneuroendocrinetumorsdevelopment |