Comprehensive analysis of an endoplasmic reticulum stress-related gene prediction model and immune infiltration in idiopathic pulmonary fibrosis

Honglan Zhu; Aiming Zhou; Menglin Zhang; Lin Pan; Xiao Wu; Chenkun Fu; Ling Gong; Wenting Yang; Daishun Liu; Yiju Cheng

doi:10.3389/fimmu.2023.1305025

Comprehensive analysis of an endoplasmic reticulum stress-related gene prediction model and immune infiltration in idiopathic pulmonary fibrosis

Front Immunol. 2024 Jan 11:14:1305025. doi: 10.3389/fimmu.2023.1305025. eCollection 2023.

Authors

Honglan Zhu^{1

2

3}, Aiming Zhou^{2

4}, Menglin Zhang^{2

5}, Lin Pan⁶, Xiao Wu⁷, Chenkun Fu², Ling Gong³, Wenting Yang¹, Daishun Liu⁸, Yiju Cheng^{2

9}

Affiliations

¹ Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
² Department of Clinical Medicine, Guizhou Medical University, Guiyang, China.
³ Department of Respiratory and Critical Care Medicine, The Third Affiliated Hospital (The First People's Hospital of Zunyi) of Zunyi Medical University, Zunyi, China.
⁴ Department of Cardiac Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
⁵ Department of Respiratory and Critical Care Medicine, The First People's Hospital of Anshun, Anshun, China.
⁶ Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Army Medical University, Chongqing, China.
⁷ Department of Respiratory and Critical Care Medicine, The Second People's Hospital of Guiyang, Guiyang, China.
⁸ Department of Clinical Medicine, Zunyi Medical University, Zunyi, China.
⁹ Department of Respiratory and Critical Care Medicine, The Fourth People's Hospital of Guiyang, Guiyang, China.

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease. This study aimed to investigate the involvement of endoplasmic reticulum stress (ERS) in IPF and explore its correlation with immune infiltration.

Methods: ERS-related differentially expressed genes (ERSRDEGs) were identified by intersecting differentially expressed genes (DEGs) from three Gene Expression Omnibus datasets with ERS-related gene sets. Gene Set Variation Analysis and Gene Ontology were used to explore the potential biological mechanisms underlying ERS. A nomogram was developed using the risk signature derived from the ERSRDEGs to perform risk assessment. The diagnostic value of the risk signature was evaluated using receiver operating characteristics, calibration, and decision curve analyses. The ERS score of patients with IPF was measured using a single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm. Subsequently, a prognostic model based on the ERS scores was established. The proportion of immune cell infiltration was assessed using the ssGSEA and CIBERSORT algorithms. Finally, the expression of ERSRDEGs was validated in vivo and in vitro via RT-qPCR.

Results: This study developed an 8-ERSRDEGs signature. Based on the expression of these genes, we constructed a diagnostic nomogram model in which agouti-related neuropeptide had a significantly greater impact on the model. The area under the curve values for the predictive value of the ERSRDEGs signature were 0.975 and 1.000 for GSE70866 and GSE110147, respectively. We developed a prognostic model based on the ERS scores of patients with IPF. Furthermore, we classified patients with IPF into two subtypes based on their signatures. The RT-qPCR validation results supported the reliability of most of our conclusions.

Conclusion: We developed and verified a risk model using eight ERSRDEGs. These eight genes can potentially affect the progression of IPF by regulating ERS and immune responses.

Keywords: bioinformatics analysis; diagnosis; endoplasmic reticulum stress (ER stress); idiopathic pulmonary fibrosis; immune filtration; prognosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Algorithms
Calibration
Endoplasmic Reticulum Stress / genetics
Humans
Idiopathic Pulmonary Fibrosis* / genetics
Reproducibility of Results

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Funds to purchase reagents were provided by the National Natural Science Foundation of China (No. 81760016) and Funds to purchase cell lines were provided by the Science and Technology Fund of Guizhou Province, China (No. Qian Ke He Ji Chu- ZK[2021] Yi Ban 347).