# Integrating bioinformatics and molecular experiments to reveal the critical role of the cellular energy metabolism-related marker PLA2G1B in COPD epithelial cells

## TL;DR

This study combines bioinformatics and experiments to show how the gene PLA2G1B affects energy metabolism and cell damage in COPD.

## Contribution

The study identifies six energy metabolism-related genes in COPD and experimentally validates the role of PLA2G1B in disease mechanisms.

## Key findings

- PLA2G1B is downregulated in COPD epithelial cells and its knockdown causes inflammation and cell death.
- Six key genes regulating cellular energy metabolism in COPD were identified and used to build a prognostic model with 81.4% accuracy.
- Bioinformatics and experimental results confirm the link between energy metabolism and COPD progression.

## Abstract

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease characterized by small airway lesions and persistent airflow limitation. Recent studies have highlighted impaired cellular energy metabolism (CEM) in COPD, although the underlying mechanisms remain incompletely understood.

This research identified cell energy metabolism-related differentially expressed genes (CEM-DEGs) by collecting CEM-associated signatures from multiple public databases and integrating these markers with data from the GEO database. Subsequently, five machine learning algorithms—Boruta, Xgboost, GBM, SVM-RFE, and LASSO—were employed to screen for key variables. Gene Set Enrichment Analysis (GSEA) and immune infiltration analysis were then performed on these key CEM-DEGs. Finally, the results of the bioinformatics analysis were verified by in vitro and in vivo experiments in combination with the single-cell data analysis results.

Bioinformatic analysis identified six critical markers (CYP1B1, CA3, AHRR, MGAM, PNMT, and PLA2G1B) that regulated CEM in the progression of COPD, from which a prognostic model was constructed using a nomogram with an area under the curve (AUC) of 0.814. Functional enrichment analysis further elucidated the intricate interplay between these CEM regulatory factors and key biological processes, including inflammation, oxidative stress, and epithelial-mesenchymal transition. Beyond that, both in vitro and in vivo experiments, along with single-cell data analysis, have conclusively verified the specific downregulation of PLA2G1B in epithelial cells derived from the COPD group. Notably, the knockdown of PLA2G1B in epithelial cells triggered inflammation, oxidative stress, and apoptosis.

This study identified six CEM-related biomarkers (CYP1B1, CA3, AHRR, MGAM, PNMT, and PLA2G1B) in COPD and established a corresponding prognostic model. Furthermore, in vitro and in vivo experiments validated the regulatory role of PLA2G1B in epithelial cell inflammation, oxidative stress, and apoptosis, thereby elucidating the mechanism underlying CEM in COPD and potentially uncovering novel therapeutic targets for drug development.