Identification of PANoptosis-related Genes for Idiopathic Pulmonary Fibrosis by Machine Learning and Molecular Subtype Analysis

Overview

Journal Sci Rep

Specialty Science

Date 2024 Oct 14

PMID 39402203

Authors

Li Wu

Yang Liu

Yifan Zhang

Rui Xu

Kaixin Bi

Jing Li

Jia Wang

Yabing Liu

Wanjin Guo

Qi Wang

Zhiqiang Chen

Affiliations

Soon will be listed here.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a severe interstitial lung disease characterized by a grim prognosis, in which various forms of cell death are significant contributors to its development. The objective of this study is to explore diagnostic biomarkers and molecular subtypes associated with PANoptosis in IPF, and to develop reliable diagnostic models based on PANoptosis-related mechanisms. The peripheral blood transcriptomic data of IPF from the Gene Expression Omnibus (GEO) database and PANoptosis-related genes from the GeneCards database were utilized to conduct differential gene expression analysis and weighted gene co-expression network analysis (WGCNA), identifying PANoptosis-related differentially expressed genes (PDEGs). We yielded 9 PDEGs and employed machine learning algorithms to identify 3 key diagnostic biomarkers for PANoptosis in IPF: MMP9, FCMR, NIBAN3. Consensus clustering algorithm was applied to recognize two PANoptosis-related subtypes. Cluster 1 exhibited higher abundance of adaptive immune response cells and significant enrichment in DNA damage and repair-related pathways. Cluster 2 exhibited greater prevalence of innate immune response cells and predominant enhancement in pathways related to lipid cholesterol metabolism and vascular remodeling. Diagnostic models were developed with the aid of clinical decision-making and a novel approach to the diagnosis and treatment for IPF.

References

Chen S, Jiang J, Li T, Huang L . PANoptosis: Mechanism and Role in Pulmonary Diseases. Int J Mol Sci. 2023; 24(20). PMC: 10607352. DOI: 10.3390/ijms242015343. View

Yanagihara T, Tsubouchi K, Zhou Q, Chong M, Otsubo K, Isshiki T . Vascular-Parenchymal Cross-Talk Promotes Lung Fibrosis through BMPR2 Signaling. Am J Respir Crit Care Med. 2023; 207(11):1498-1514. DOI: 10.1164/rccm.202109-2174OC. View

Chen R, Dai J . Lipid metabolism in idiopathic pulmonary fibrosis: From pathogenesis to therapy. J Mol Med (Berl). 2023; 101(8):905-915. DOI: 10.1007/s00109-023-02336-1. View

Oldham J, Huang Y, Bose S, Ma S, Kim J, Schwab A . Proteomic Biomarkers of Survival in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2023; 209(9):1111-1120. PMC: 11092951. DOI: 10.1164/rccm.202301-0117OC. View

Wolters P, Collard H, Jones K . Pathogenesis of idiopathic pulmonary fibrosis. Annu Rev Pathol. 2013; 9:157-79. PMC: 4116429. DOI: 10.1146/annurev-pathol-012513-104706. View

Langfelder P, Horvath S . WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008; 9:559. PMC: 2631488. DOI: 10.1186/1471-2105-9-559. View

Neys S, Heukels P, van Hulst J, Rip J, Wijsenbeek M, Hendriks R . Aberrant B Cell Receptor Signaling in Naïve B Cells from Patients with Idiopathic Pulmonary Fibrosis. Cells. 2021; 10(6). PMC: 8226954. DOI: 10.3390/cells10061321. View

Cheng P, Li S, Chen H . Macrophages in Lung Injury, Repair, and Fibrosis. Cells. 2021; 10(2). PMC: 7923175. DOI: 10.3390/cells10020436. View

Joannes A, Morzadec C, Duclos M, Gutierrez F, Chiforeanu D, Le Naoures C . Arsenic trioxide inhibits the functions of lung fibroblasts derived from patients with idiopathic pulmonary fibrosis. Toxicol Appl Pharmacol. 2022; 441:115972. DOI: 10.1016/j.taap.2022.115972. View

10.

Pan H, Pan J, Li P, Gao J . Characterization of PANoptosis patterns predicts survival and immunotherapy response in gastric cancer. Clin Immunol. 2022; 238:109019. DOI: 10.1016/j.clim.2022.109019. View

11.

Prele C, Miles T, Pearce D, ODonoghue R, Grainge C, Barrett L . Plasma cell but not CD20-mediated B-cell depletion protects from bleomycin-induced lung fibrosis. Eur Respir J. 2022; 60(5). PMC: 9684624. DOI: 10.1183/13993003.01469-2021. View

12.

Choi S, Wang H, Tian L, Murakami Y, Shin D, Borrego F . Mouse IgM Fc receptor, FCMR, promotes B cell development and modulates antigen-driven immune responses. J Immunol. 2012; 190(3):987-96. PMC: 3552009. DOI: 10.4049/jimmunol.1202227. View

13.

Nguyen X, Lang P, Lang K, Adam D, Fattakhova G, Foger N . Toso regulates the balance between apoptotic and nonapoptotic death receptor signaling by facilitating RIP1 ubiquitination. Blood. 2011; 118(3):598-608. DOI: 10.1182/blood-2010-10-313643. View

14.

Tang J, Yao C, Liu Y, Yuan J, Wu L, Hosoi K . Arsenic trioxide induces expression of BCL-2 expression via NF-κB and p38 MAPK signaling pathways in BEAS-2B cells during apoptosis. Ecotoxicol Environ Saf. 2021; 222:112531. DOI: 10.1016/j.ecoenv.2021.112531. View

15.

Kubagawa H, Carroll M, Jacob C, Lang K, Lee K, Mak T . Nomenclature of Toso, Fas apoptosis inhibitory molecule 3, and IgM FcR. J Immunol. 2015; 194(9):4055-7. DOI: 10.4049/jimmunol.1500222. View

16.

Chen J, Jin Z, Zhang S, Zhang X, Li P, Yang H . Arsenic trioxide elicits prophylactic and therapeutic immune responses against solid tumors by inducing necroptosis and ferroptosis. Cell Mol Immunol. 2022; 20(1):51-64. PMC: 9794749. DOI: 10.1038/s41423-022-00956-0. View

17.

He Y, Deng J, Zhou C, Jiang S, Zhang F, Tao X . Ursodeoxycholic acid alleviates sepsis-induced lung injury by blocking PANoptosis via STING pathway. Int Immunopharmacol. 2023; 125(Pt B):111161. DOI: 10.1016/j.intimp.2023.111161. View

18.

Samarelli A, Masciale V, Aramini B, Colo G, Tonelli R, Marchioni A . Molecular Mechanisms and Cellular Contribution from Lung Fibrosis to Lung Cancer Development. Int J Mol Sci. 2021; 22(22). PMC: 8624248. DOI: 10.3390/ijms222212179. View

19.

Kanehisa M, Furumichi M, Sato Y, Kawashima M, Ishiguro-Watanabe M . KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res. 2022; 51(D1):D587-D592. PMC: 9825424. DOI: 10.1093/nar/gkac963. View

20.

Greener J, Kandathil S, Moffat L, Jones D . A guide to machine learning for biologists. Nat Rev Mol Cell Biol. 2021; 23(1):40-55. DOI: 10.1038/s41580-021-00407-0. View