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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders: Autoinflammatory Disorders
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1458341
This article is part of the Research Topic New Targets and Strategies for the Prevention and Treatment of Organ Fibrosis, Volume III View all 9 articles

Contribution of cuproptosis and immune -related genes to idiopathic pulmonary fibrosis disease

Provisionally accepted
Jin Liang Jin Liang 1*Jing Wang Jing Wang 2,3*Chengji Jin Chengji Jin 2*JIA LI JIA LI 4Qiaoyu Li Qiaoyu Li 4*Lipeng Zhang Lipeng Zhang 4*Shaomao Zheng Shaomao Zheng 2*Qiong Feng Qiong Feng 2*Yongji Li Yongji Li 5*Yu Zheng Yu Zheng 4*Qiuli Nie Qiuli Nie 4*
  • 1 Department of Rheumatology and Immunology, The Second Affiliated Hospital of Hainan Medical University, Hai Kou, China
  • 2 Department of Respiratory Medicine, Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, China
  • 3 Key Laboratory of Tropical Translation Medicine of Ministry of Education, Hainan Medical University, Haikou, Hainan Province, China
  • 4 Second Affiliated Hospital of Hainan Medical University, Haikou, China
  • 5 Department of Thoracic Surgery, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, China

The final, formatted version of the article will be published soon.

    Background: Idiopathic pulmonary fibrosis (IPF) is a degenerative respiratory condition characteriz ed by significant mortality rates and a scarcity of available treatment alternatives. Cuproptosis is a no vel copper-induced form of cell death. The aim of this study was to investigate the value of cuproptos is-related hub genes in the diagnosis of patients with IPF. Meanwhile, this paper also uses multiple bioinformatics analyses to find immune-related biomarkers associated with the diagnosis of IPF, whi ch can provide more comprehensive assistance in the subsequent treatment of IPF.Methods: Four microarray datasets were selected for screening from the Gene Expression Omnibus (GEO) collection. Differentially expressed genes(DEGs) associated with IPF were analyzed. Meanw hile, we employed weighted gene co-expression network analysis (WGCNA) to identify the DEGs m ost associated with IPF. Ultimately, we analysed five cuproptosis-related hub genes , and tested the diagnostic value of five genes in IPF in both the training and validation sets. Additionally, four immu ne -related hub genes were screened using protein-protein interaction (PPI) network and evaluated by using receiver operating characteristic (ROC) curve. Lastly, Single-cell RNA-seq was utilized to fur ther reveal differential gene distribution.We identified 92 DEGs in total. Machine learningBioinformatic analysis has pinpointed five genes li nked to cuproptosis-related identified as candidate biomarkers. Including three up-regulated genes, C FH, STEAP1 and HDC, and two down-regulated genes, NUDT16 and FMO5. It was confirmed that t he diagnostic effect of the five genes in the cohort was also predicted to be accurate. On the other ha nd, we identified four immune-related hub genes(CXCL12,CXCR2,CTSG,SPP1) that also performed better in diagnosing IPF, includi ng 0.90 for CXCL12 AUROC. Finally, our single-cell sequencing data demonstrate that in patients with IPF, CXCL12 is highly expressed in the endothelial cell subset (ECs), whereas SPP1 exhibited high levels of expression in multiple cellular populations. The CTSG expression displayed statistically significant variance in monocyte macrophages. However,CXCR2 is predominantly expressed in the neutrophil population of the normal group.

    Keywords: Idiopathic Pulmonary Fibrosis Disease, cuproptosis -related genes, immune -related genes, Immune infiltration, machine learning, single-cell RNA-seq

    Received: 02 Jul 2024; Accepted: 14 Jan 2025.

    Copyright: © 2025 Liang, Wang, Jin, LI, Li, Zhang, Zheng, Feng, Li, Zheng and Nie. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Jin Liang, Department of Rheumatology and Immunology, The Second Affiliated Hospital of Hainan Medical University, Hai Kou, China
    Jing Wang, Department of Respiratory Medicine, Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, China
    Chengji Jin, Department of Respiratory Medicine, Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, China
    Qiaoyu Li, Second Affiliated Hospital of Hainan Medical University, Haikou, China
    Lipeng Zhang, Second Affiliated Hospital of Hainan Medical University, Haikou, China
    Shaomao Zheng, Department of Respiratory Medicine, Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, China
    Qiong Feng, Department of Respiratory Medicine, Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, China
    Yongji Li, Department of Thoracic Surgery, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, China
    Yu Zheng, Second Affiliated Hospital of Hainan Medical University, Haikou, China
    Qiuli Nie, Second Affiliated Hospital of Hainan Medical University, Haikou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.