Predictive investigation of idiopathic pulmonary fibrosis subtypes based on cellular senescence-related genes for disease treatment and management

Changqing Yang; Ziqi Han; Wenyu Zhan; Yubao Wang; Jing Feng

doi:10.3389/fgene.2023.1157258

Predictive investigation of idiopathic pulmonary fibrosis subtypes based on cellular senescence-related genes for disease treatment and management

Front Genet. 2023 Mar 24:14:1157258. doi: 10.3389/fgene.2023.1157258. eCollection 2023.

Authors

Changqing Yang¹, Ziqi Han¹, Wenyu Zhan¹, Yubao Wang¹, Jing Feng¹

Affiliation

¹ Respiratory Department, Tianjin Medical University General Hospital, Tianjin, China.

Abstract

Background: Idiopathic pulmonary fibrosis (IPF), a chronic, progressive lung disease characterized by interstitial remodeling and tissue destruction, affects people worldwide and places a great burden on society. Cellular senescence is thought to be involved in the mechanisms and development of IPF. The aim of this study was to predictively investigate subtypes of IPF according to cellular senescence-related genes and their correlation with the outcome of patients with IPF, providing possible treatment and management options for disease control. Methods: Gene expression profiles and follow-up data were obtained from the GEO database. Senescence-related genes were obtained from the CSGene database and analyzed their correlation with the outcome of IPF. A consensus cluster was constructed to classify the samples based on correlated genes. The GSVA and WGCNA packages in R were used to calculate the immune-related enriched fractions and construct gene expression modules, respectively. Metascape and the clusterProfiler package in R were used to enrich gene functions. The ConnectivityMap was used to probe suitable drugs for potential treatment. Results: A total of 99 cellular senescence-related genes were associated with IPF prognosis. Patients with IPF were divided into two subtypes with significant prognostic differences. Subtype S2 was characterized by enhanced fibrotic progression and infection, leading to acute exacerbation of IPF and poor prognosis. Finally, five cellular senescence-related genes, TYMS, HJURP, UBE2C, BIRC5, and KIF2C, were identified as potential biomarkers in poor prognostic patients with IPF. Conclusion: The study findings indicate that cellular senescence-related genes can be used to distinguish the prognosis of patients with IPF. Among them, five genes can be used as candidate biomarkers to predict patients with a poor prognostic subtype for which anti-fibrosis and anti-infection treatments could be suitable.

Keywords: cellular senescence; idiopathic pulmonary fibrosis; prognosis; subtype; treatment.

Grants and funding

This study was supported by the National Science and Technology Major Project of China (No. 2018ZX10305409001-001), National Natural Science Foundation of China (81970083, 81270144, 81570084, and 30800507 to JF), the National Key Technology R&D Program, China (2015BAI12B00 to JF), and the Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-008A).