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Study on the common mechanisms of gastroesophageal reflux disease and interstitial lung disease.

Wen Zhang,Qi Cai,Liusheng You,Wei Zhang,Xiujin Zheng,Chenglin Jiang,Changdan Chen

Published 2025 in Human Immunology

ABSTRACT

OBJECTIVE Interstitial lung disease (ILD) and gastroesophageal reflux disease (GERD) have complex interactions and can exacerbate severity of each other. This study aimed to screen shared genes between ILD and GERD and explore their common mechanisms and clinical value. METHODS We obtained microarray datasets of ILD and GERD from public databases. Shared genes were screened by differential expression analysis and Venn analysis. Hub genes were screened from shared genes using the protein-protein interaction (PPI) network analysis. The ssGSEA algorithm was utilized to estimate immune infiltration level of ILD and GERD, and correlation of hub genes with immune cell infiltration was studied. Finally, potential drugs that may act on hub genes were screened using DSigDB. RESULTS 52 shared genes were obtained through Venn analysis. PPI network analysis identified 10 hub genes (BMP4, NT5E, PPARG, EPCAM, DPP4, KLF2, MMP1, AGR2, ADAMTS1, GATA6) that may have diagnostic performance (p < 0.05). The results of immune infiltration showed that hub genes were highly linked to multiple immune cell infiltrations (p < 0.05). In addition, we identified 5 potential drugs. Notably, thioridazine may target 5 hub genes (MMP1, AGR2, KLF2, ADAMTS1, and PPARG) simultaneously (p < 0.05) and had the potential to be a novel therapeutic drug. CONCLUSION In summary, we have screened out the hub genes with diagnostic value in ILD and GERD, and also revealed the close relationship between the hub genes and the disease immune microenvironment, providing new research directions for the common mechanism and interaction of the two diseases.

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