Development and Validation of a Novel Gene Signature for Predicting the Prognosis of Idiopathic Pulmonary Fibrosis Based on Three Epithelial-Mesenchymal Transition and Immune-Related Genes.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35559024", "kind": "science-record", "revision": 5, "content_hash": "sha256:9f35104665ac4ef7d3e6d76f00af3646386ed8bb2e49c46dd4c7e2b5db53ef9d", "created_at": "2026-11-01T18:14:27Z", "updated_at": "2026-11-01T22:49:02Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Development and Validation of a Novel Gene Signature for Predicting the Prognosis of Idiopathic Pulmonary Fibrosis Based on Three Epithelial-Mesenchymal Transition and Immune-Related Genes.", "doi": "10.3389/fgene.2022.865052", "pmid": "35559024", "authors": ["Jiafeng Zheng", "Hanquan Dong", "Tongqiang Zhang", "Jing Ning", "Yongsheng Xu", "Chunquan Cai"], "journal": "Frontiers in genetics", "year": 2022, "abstract": "Background: Increasing evidence has revealed that epithelial-mesenchymal transition (EMT) and immunity play key roles in idiopathic pulmonary fibrosis (IPF). However, correlation between EMT and immune response and the prognostic significance of EMT in IPF remains unclear. Methods: Two microarray expression profiling datasets (GSE70866 and GSE28221) were downloaded from the Gene Expression Omnibus (GEO) database. EMT- and immune-related genes were identified by gene set variation analysis (GSVA) and the Estimation of STromal and Immune cells in MAlignant Tumors using Expression data (ESTIMATE) algorithm. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to investigate the functions of these EMT- and immune-related genes. Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were used to screen prognostic genes and establish a gene signature. Gene Set Enrichment Analysis (GSEA) and Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) were used to investigate the function of the EMT- and immune-related signatures and correlation between the EMT- and immune-related signatures and immune cell infiltration. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to investigate the mRNA expression of genes in the EMT- and immune-related signatures. Results: Functional enrichment analysis suggested that these genes were mainly involved in immune response. Moreover, the EMT- and immune-related signatures were constructed based on three EMT- and immune-related genes (IL1R2, S100A12, and CCL8), and the K-M and ROC curves presented that the signature could affect the prognosis of IPF patients and could predict the 1-, 2-, and 3-year survival well. Furthermore, a nomogram was developed based on the expression of IL1R2, S100A12, and CCL8, and the calibration curve showed that the nomogram could visually and accurately predict the 1-, 2-, 3-year survival of IPF patients. Finally, we further found that immune-related pathways were activated in the high-risk group of patients, and the EMT- and immune-related signatures were associated with NK cells activated, macrophages M0, dendritic cells resting, mast cells resting, and mast cells activated. qRT-PCR suggested that the mRNA expression of IL1R2, S100A12, and CCL8 was upregulated in whole blood of IPF patients compared with normal samples. Conclusion: IL1R2, S100A12, and CCL8 might play key roles in IPF by regulating immune response and could be used as prognostic biomarkers of IPF.", "claims": [{"id": "claim-method", "statement": "Finally, differentially expressed genes (DEGs) between the high-EMT score and low-EMT score groups were identified using limma 3.44.3 package in R (doi: 10.1093/nar/gkv007) and were defined as EMT-related genes.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35559024", "locator": "sections[4] \"Identification of Epithelial-Mesenchymal Transition-Related Genes\" paragraph 2", "quote": "Finally, differentially expressed genes (DEGs) between the high-EMT score and low-EMT score groups were identified using limma 3.44.3 package in R (doi: 10.1093/nar/gkv007) and were defined as EMT-related genes."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found at: https://github.com/zhengjiafenglab/IPF.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35559024", "locator": "sections[20] \"Data Availability Statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found at: https://github.com/zhengjiafenglab/IPF."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using limma to analyze the batch-corrected GSE70866 and GSE28221 microarray datasets from GEO, the study identified 230 EMT-related DEGs and 199 immune-related DEGs, with 13 genes overlapping between the two sets.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35559024", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Two microarray expression profiling datasets (GSE70866 and GSE28221) were downloaded from the Gene Expression Omnibus (GEO) database."}, {"asset": "source:pmid:35559024", "locator": "sections[13] \"Identification of Epithelial-Mesenchymal Transition-Related Genes\" paragraph 2", "quote": "Next, a total of 230 DEGs (Supplementary Material S2), including 228 upregulated genes and two downregulated genes in patients of the EMT score-high group compared with patients in the immune score-low group, were identified and defined as EMT-related genes (Figures 2A,B)."}, {"asset": "source:pmid:35559024", "locator": "sections[14] \"Identification of Epithelial-Mesenchymal Transition- and Immune-Related Genes\" paragraph 2", "quote": "Subsequently, a total of 199 DEGs (Supplementary Material S3), including 195 upregulated genes and four downregulated genes in patients of the immune score-high group compared with patients in the immune score-low group, were identified and defined as immune-related genes (Figures 4A,B)."}, {"asset": "source:pmid:35559024", "locator": "sections[14] \"Identification of Epithelial-Mesenchymal Transition- and Immune-Related Genes\" paragraph 2", "quote": "After overlapping EMT-and immune-related genes, 13 EMT- and immune-related genes were identified (Figure 4C, Supplementary Table S2)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Using limma to analyze the batch-corrected GSE70866 and GSE28221 microarray datasets from GEO, the study identified 230 EMT-related DEGs and 199 immune-related DEGs, with 13 genes overlapping between the two sets.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:35559024"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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