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Background <p>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.</p> Method <p>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.</p> Results <p>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.</p> Conclusions <p>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.</p>

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The role of immune cells phenotype in neuroendocrine tumors development

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月3日

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  • Jie Qiao,
  • Yi-Wen Wu,
  • Yuan-You Wang,
  • Jing-Jing Huang,
  • Peng-Fei Shan

摘要

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.