Research Paper Volume 16, Issue 11 pp 10063—10073

The causal role of immune cells on lung cancer: a bi-directional Mendelian randomization (MR) study

Hongyu Zhu1, *, , Caihua Chen1, *, , Haixie Guo1, , Bo Zhang1, , Quanteng Hu1, ,

  • 1 Department of Thoracic Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou 317000, Zhejiang, China
* Equal contribution

Received: January 10, 2024       Accepted: April 10, 2024       Published: June 12, 2024      

https://doi.org/10.18632/aging.205917
How to Cite

Copyright: © 2024 Zhu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Immune cells play a vital role in the development and progression of lung cancer (LC). We aimed to explore the causal role of immune cells in LC with Mendelian randomization (MR) study. Summary statistic data used in the study were obtained from genome-wide association studies (GWAS). A comprehensive two-sample MR was carried out to explore the causal role of 731 immune cell traits (ICTs) in LC, Non-small cell lung cancer (NSCLC), and Small cell lung cancer (SCLC). An inverse-variance weighted (IVW) approach was applied to present the MR estimates. The heterogeneity test was performed using Cochran’s Q statistic. MR-Egger intercept test and MR-PRESSO were utilized for the pleiotropy test. MR showed that 15, 31, and 11 ICTs had protective effects on LC, NSCLC, and SCLC, respectively, and 12, 31, and 11 ICTs had adverse effects on LC, NSCLC, and SCLC, respectively. Of note, CD3 on CD28+ CD4+ in the Treg panel could significantly increase the risk of LC, as well as NSCLC and SCLC. Moreover, the MR results revealed that LC was vital in IgD on IgD+ in the B cell panel and NSCLC on CCR2 on CD14- CD16- in the Monocyte panel. Our study revealed multiple close connections between immune cells and LC.

Abbreviations

AC: absolute counts; CI: confidence interval; GWAS: genome-wide association studies; ICI: immune checkpoint inhibitor; IVs: instrumental variables; IVW: inverse variance weighted; LC: lung cancer; MFI: median fluorescence intensities; MR: Mendelian randomization; MR-PRESSO: MR pleiotropy residual sum and outlier; MP: morphological parameters; NSCLC: non-small cell lung cancer; OR: odds ratio; RC: relative counts; SCLC: small cell lung cancer; SNP: single nucleotide polymorphism; TBNK: B cells, natural killer cells, T cells.