# Chromosome structural variation analysis reveals lung cancer-associated gene regulatory networks in rheumatoid arthritis patients

## TL;DR

This study explores how chromosomal structural variations relate to rheumatoid arthritis and lung cancer, identifying key genetic pathways involved.

## Contribution

The study identifies disease-specific chromosomal structural variations and their associated pathways in rheumatoid arthritis and lung cancer.

## Key findings

- Cell size regulation and axon guidance mutations were common across all disease groups.
- Protein deubiquitination was uniquely mutated in rheumatoid arthritis with lung cancer.
- Negative regulation of stroma and protein catabolism was mutated in rheumatoid arthritis with interstitial lung disease.

## Abstract

Chromosomal structural variations (CSVs) that comprise multiple gene mutations are important determinants for multiple diseases. However, the relationship between CSVs, rheumatoid arthritis (RA), and lung cancer is not well understood.

In this study, we analyzed CSV associations and differences between RA and RA with lung cancer (RA LC) using genome sequencing, with RA-associated interstitial lung disease (RA ILD) as a disease control. First, we analyzed the CSVs of each individual. Then, we identified common CSVs within each disease group and finally analyzed specific CSVs between different diseases. Gene Ontology/KEGG terms, canonical pathways, and feature gene sets were used for the functional annotation and analysis of CSV-related pathways.

Cell size regulation and axon guidance were mutated in all disease groups. Protein deubiquitination was mutated in RA LC, while the negative regulation of extractable stroma and protein catabolism was mutated in RA ILD. Characterization of clinical data also revealed correlations with these specific pathways.

This study identifies common and specific CSVs and associated pathways for RA, LC, and ILD, uncovering key genetic factors that provide new insights into their diagnosis and treatment.

The online version contains supplementary material available at 10.1186/s12920-025-02273-7.