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

## TL;DR

This study suggests that higher CD300C gene expression may reduce lung adenocarcinoma risk, possibly by influencing CD62L⁻ monocytes.

## Contribution

The study introduces a novel CD300C–CD62L⁻ monocyte axis as a potential mechanism for lung adenocarcinoma susceptibility.

## Key findings

- Higher CD300C expression is associated with reduced lung adenocarcinoma risk.
- CD300C expression is positively linked to CD62L⁻ monocytes, which are inversely associated with lung adenocarcinoma.
- The mediated effect of CD300C on lung adenocarcinoma via CD62L⁻ monocytes accounts for 22.92% of the total association.

## Abstract

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.

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.

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.

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.

The online version contains supplementary material available at 10.1007/s12672-026-04481-8.