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Background <p>This exploratory, hypothesis-generating study aimed to evaluate the potential genetically informed association between <i>CD300C</i> gene expression and lung adenocarcinoma (LUAD) risk, and to investigate the possible mediating role of CD62L⁻ monocytes using a multi-omics Mendelian randomization (MR) framework.</p> Methods <p>We integrated LUAD GWAS summary statistics, peripheral blood eQTL and pQTL data, and transcriptomic profiles. Candidate genes were prioritized by overlapping evidence from eQTL-MR, pQTL-MR, and expression analyses. A three-step Mendelian randomization model estimated the total, mediated, and direct effects of <i>CD300C</i> expression on LUAD risk via CD62L⁻ monocytes.</p> Results <p><i>CD300C</i> was the only gene consistently associated with LUAD across all omics stages. Higher <i>CD300C</i> expression was associated with reduced LUAD risk (<i>β</i> = − 0.030, OR = 0.97, 95% CI: 0.942–0.999), while the proportion of CD62L⁻ monocytes was also inversely associated with LUAD (<i>β</i> = − 0.086, OR = 0.91, 95% CI: 0.855–0.982). <i>CD300C</i> expression was positively associated with CD62L⁻ monocytes (<i>β</i> = 0.008, OR = 1.082, 95% CI: 1.029–1.139). The estimated mediated effect was β = -0.007, accounting for 22.92% of the total association.</p> Conclusions <p>Our findings provide preliminary, genetically informed evidence that higher <i>CD300C</i> expression may be nominally associated with reduced LUAD risk, potentially in part through CD62L⁻ monocytes. Given the limited statistical power and the lack of significance after multiple-testing correction, these findings should be interpreted as exploratory and hypothesis-generating. They nominate the <i>CD300C</i>–CD62L⁻ monocyte axis as a hypothesis for future investigation.</p>

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CD300C reduces lung adenocarcinoma susceptibility through regulation of CD62L⁻ monocytes: a Mendelian randomization study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月24日

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  • Huiling Chen,
  • Zhichun Xue,
  • Liwen Huang,
  • Ying Zeng,
  • Meiyan Tang,
  • Kunhuang Han,
  • Jia Chen,
  • Xinyu Deng,
  • Guiju Fang

摘要

Background

This exploratory, hypothesis-generating study aimed to evaluate the potential genetically informed association between CD300C gene expression and lung adenocarcinoma (LUAD) risk, and to investigate the possible mediating role of CD62L⁻ monocytes using a multi-omics Mendelian randomization (MR) framework.

Methods

We integrated LUAD GWAS summary statistics, peripheral blood eQTL and pQTL data, and transcriptomic profiles. Candidate genes were prioritized by overlapping evidence from eQTL-MR, pQTL-MR, and expression analyses. A three-step Mendelian randomization model estimated the total, mediated, and direct effects of CD300C expression on LUAD risk via CD62L⁻ monocytes.

Results

CD300C was the only gene consistently associated with LUAD across all omics stages. Higher CD300C expression was associated with reduced LUAD risk (β = − 0.030, OR = 0.97, 95% CI: 0.942–0.999), while the proportion of CD62L⁻ monocytes was also inversely associated with LUAD (β = − 0.086, OR = 0.91, 95% CI: 0.855–0.982). CD300C expression was positively associated with CD62L⁻ monocytes (β = 0.008, OR = 1.082, 95% CI: 1.029–1.139). The estimated mediated effect was β = -0.007, accounting for 22.92% of the total association.

Conclusions

Our findings provide preliminary, genetically informed evidence that higher CD300C expression may be nominally associated with reduced LUAD risk, potentially in part through CD62L⁻ monocytes. Given the limited statistical power and the lack of significance after multiple-testing correction, these findings should be interpreted as exploratory and hypothesis-generating. They nominate the CD300C–CD62L⁻ monocyte axis as a hypothesis for future investigation.