Unravelling genetic commonalities between idiopathic pulmonary fibrosis and gastroesophageal reflux disease: A bioinformatics exploration

Abstract

Background

Idiopathic pulmonary fibrosis (IPF) and gastroesophageal reflux disease (GERD) are chronic conditions that frequently co-occur, yet their genetic correlation remains underexplored.

Methods

This study utilized publicly available datasets (GSE150910 and GSE226303) from the NCBI-GEO database to identify common differentially expressed genes (DEGs) between IPF and GERD. DEGs were analyzed using DESeq2 and GEO2R, with hub genes identified via cytoHubba algorithms (MCC, MNC, DMNC). Subsequently, network interactions were analyzed with GeneMania, while pathway interactions were explored using the Enrichr tool. Potential drug targets were identified using DGIdb, with ADMET properties evaluated using SWISSADME and toxicity assessed via Protox-II. Molecular docking of the drug to target protein was performed using AutoDock Vina to predict the binding affinities.

Results

A total of 52 overlapping DEGs (51 up-regulated, 1 down-regulated) were identified between IPF and GERD, with nine hub genes (MUC5AC, RGS2, AGR2, LIF, CXCL6, CXCL8, SULT1E1, RGS1, and IL1B) selected through topological analysis. RGS1 and LIF showed the highest diagnostic potential, supported by distinct correlation patterns in gene expression. Haloperidol, identified via DGIdb, interacts strongly with RGS2, confirmed by docking analysis (−7.5 kcal/mol). ADMET analysis demonstrated haloperidol's oral bioavailability and adherence to Lipinski's rules, while Protox-II classified it as toxicity class-3.

Conclusions

This study identifies nine common hub genes and highlights the association of the IL-10 signaling pathway in both IPF and GERD. Haloperidol emerged as a potential therapeutic drug for IPF patients with GERD, showing significant interaction with RGS2.