Background: Though IPF and RA-ILD are separate diseases, they share similar clinical manifestations, imaging characteristics, and genetic features. Recently, researchers have found that they have some associations in pathogenesis [1]. Exploring the common hub genes in IPF and RA-UIP through bioinformatics analysis may contribute to further understanding their mutual biological pathways. Our research offers valuable insights into the underlying genetic mechanisms and therapeutic targets of IPF and RA-UIP.

Objectives: The study aims at exploring common hub genes and pathways in idiopathic pulmonary fibrosis (IPF) and rheumatoid arthritis-associated usual interstitial pneumonia (RA-UIP) through integrated bioinformatics analyses.

Methods: The GSE199152 dataset was acquired from the GEO database. The identification of overlapping DEGs in IPF and RA-UIP was carried out through the R language. PPI network analysis and module analysis were applied to filter mutual hub genes in the two diseases using Cytoscape software. GO and KEGG analyses were also conducted to analyze the biological functions of the overlapped DEGs, while GSEA was performed to investigate the shared possible biological pathways of the common key genes. The diagnostic value of key genes was assessed with R language, and the mRNA expression levels of these genes were verified in blood samples collected from patients and healthy controls by the use of qRT-PCR.

Results: 199 overlapped DEGs in the two diseases were identified, containing 143 upregulated and 56 downregulated genes. Four common hub genes (THBS2, TIMP1, POSTN and CD19) were screened. Enrichment analyses showed that the abnormal expressions of DEGs and hub genes may be connected with the onset of IPF and RA-UIP by regulating the progression of fibrosis. The qRT-PCR results manifested that the mRNA expression levels of hub genes were in accordance with the findings obtained from the bioinformatics analysis.

Conclusion: Though IPF and RA-UIP are distinct diseases, they may to some extent have mutual pathogenesis in the development of fibrosis. THBS2, TIMP1, POSTN, and CD19 may be the potential biomarkers of IPF and RA-UIP, and intervention on related pathways of these genes could offer new strategies for the treatment of IPF and RA-UIP.

REFERENCES: [1] Matson S, Lee J, Eickelberg O. Two sides of the same coin? A review of the similarities and differences between idiopathic pulmonary fibrosis and rheumatoid arthritis-associated interstitial lung disease. Eur Respir J. 2021;57(5):2002533. Published 2021 May 13. DOI:10.1183/13993003.02533-2020.

[2] Sgalla G, Biffi A, Richeldi L. Idiopathic pulmonary fibrosis: Diagnosis, epidemiology and natural history. Respirology. 2016;21(3):427-437. DOI:10.1111/resp.12683.

[3] Sgalla G, Iovene B, Calvello M, Ori M, Varone F, Richeldi L. Idiopathic pulmonary fibrosis: pathogenesis and management. Respir Res. 2018;19(1):32. Published 2018 Feb 22. DOI:10.1186/s12931-018-0730-2.

[4] Cavagna L, Monti S, Grosso V, et al. The multifaceted aspects of interstitial lung disease in rheumatoid arthritis. Biomed Res Int. 2013;2013:759760. DOI:10.1155/2013/759760.

[5] Subramanian A, Tamayo P, Mootha VK, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102(43):15545-15550. DOI:10.1073/pnas.0506580102.

Acknowledgements: NIL.

Disclosure of Interests: None declared.