# Single cell atlas of the comorbidity mechanism between chronic obstructive pulmonary disease and lung adenocarcinoma: a study of multi-omics combined analysis

## TL;DR

This study explores how COPD and lung adenocarcinoma are linked at the molecular level using multi-omics data to identify shared genes and potential treatments.

## Contribution

Identifies FCRLA, GREM1, and MMP9 as shared inflammation-related genes linking COPD and LUAD through multi-omics and single-cell analysis.

## Key findings

- FCRLA, GREM1, and MMP9 are upregulated and involved in immune regulation and ECM remodeling in both COPD and LUAD.
- Single-cell analysis shows these genes are expressed in B cells, T cells, and monocytes.
- Epigenetic and RNA-level regulation mechanisms were identified, along with candidate drugs.

## Abstract

Chronic obstructive pulmonary disease (COPD) is a recognized risk factor for lung adenocarcinoma (LUAD), but the molecular mechanisms behind this association are still unclear. This study aims to reveal shared key genes and pathways involved in both COPD and LUAD, and identify potential biomarkers and therapeutic targets.

Two-sample Mendelian randomization (MR) analysis using Genome-Wide Association Study (GWAS) data was performed to evaluate genetic causality. Differential expression analysis was performed on GSE76925 (COPD) and GSE116959 (LUAD), followed by LASSO regression, enrichment analysis, immune cell infiltration analysis, RNA modification analysis, competing endogenous RNA (ceRNA) network construction, and drug sensitivity prediction. Single-cell RNA sequencing data (GSE270667, GSE189357) were used to explore cell-type-specific expression, and qPCR was performed to validate gene expression in patient blood samples.

MR confirmed the genetic relationship between COPD and LUAD. Three key genes (FCRLA, GREM1, and MMP9) were significantly upregulated and involved in immune regulation, extracellular matrix (ECM) remodeling, and the PI3K-Akt signaling pathway. Single-cell analysis revealed that these genes were specifically expressed in B cells, T cells, and monocytes. Multiple omics analyses indicated epigenetic and RNA level regulation. Several candidate drugs have been identified.

FCRLA, GREM1, and MMP9 are inflammation-associated genes that may link the pathobiology of COPD and LUAD, and serve as valuable biomarkers with therapeutic potential in high-risk populations.