Investigation Diagnostic Gene Markers and Immune Infiltration in Idiopathic Pulmonary Fibrosis

Abstract Objective: Idiopathic pulmonary fibrosis (IPF) is a difficult to cure and low survival lung disease, and the pathogenesis has not been elucidated clearly. This study is to explore the potential hub genes in IPF and explore their role in the progression of IPF with immune cell infiltration, providing evidence support for potential diagnostic markers and targets of IPF. Method: Download the dataset GSE10667 from the GEO database to identify differentially expressed genes (DEG) between IPF patients and the normal population. Exploring hub genes related to IPF using differential expression analysis and Weighted correlation network analysis (WGCNA). Establish a Nomogram model and ROC (Receiver Operating Characteristic) curve to evaluate the diagnostic effectiveness of hub genes. Apply Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway-based enrichment analysis to explore the potential roles of these hub genes. Discover key networks of genes in protein level by Protein-Protein Interaction Networks (PPI) networks. And investigate the relationship between key gene MMP2(metallopeptidase 2) and immune infiltration. Finally, based on Genome-wide association study (GWAS), a Mendelian randomization study was conducted to determine the causal relationship between MMP2 and IPF. Result:A total of 486 DEGs were identified in IPF patients. Gene co expression network was established by WGCNA to screen the highest correlation module. And The genes in it were mainly enriched in extracellular matrix （ECM ）formation, cell aging, endoplasmic reticulum stress, and metalloproteinase activation signaling pathways. Cross the genes in the DEG related modules with WGCNA traits to obtain the core hub genes. Then, key genes COL1A1, COL3A1, COL1A2, POSTN, MMP2 were found through the PPI. The nomogram was established to verify the risk of disease occurrence, and the ROC was applied to demonstrate the accuracy of the model and shows that five hub genes are potential biomarkers for IPF. Finally, we selected MMP2 and found a causal relationship with the occurrence and prognosis of IPF through Mendelian randomization (MR)studies, as well as immune cell infiltration in IPF. Conclusion: We have identified the pivot gene MMP2 associated with IPF, which may play a key role in the progression of IPF. And may play an significant role in the pre symptom diagnosis of IPF, providing new therapeutic targets, and predicting prognosis.