Developing an IPF Prognostic Model and Screening for Key Genes Based on Cold Exposure-Related Genes Using...

Area of Science:

• Environmental Health
• Pulmonary Medicine
• Bioinformatics

Background:

• Cold exposure impacts respiratory diseases, but its role in idiopathic pulmonary fibrosis (IPF) is unclear.
• Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with significant unmet needs.
• Understanding environmental factors like cold exposure is crucial for IPF management.

Purpose of the Study:

• To investigate the potential link between cold exposure and idiopathic pulmonary fibrosis (IPF).
• To identify cold exposure-related genes (CERGs) associated with IPF.
• To develop a prognostic model for IPF based on CERGs.

Main Methods:

• RNA-Seq data from cold-exposed mice and cross-species orthologous gene conversion to identify 151 CERGs.
• Consensus clustering to stratify IPF patients into subgroups with distinct clinical features.
• Univariate, multivariate, and Lasso-Cox regression analyses to establish a nine-gene prognostic model.

Main Results:

• IPF patients were classified into two subgroups with significant differences in hypoxia, EMT, GAP scores, immune infiltration, and mortality.
• A nine-gene prognostic model based on CERGs demonstrated superior predictive accuracy (AUCs: 0.81-0.91) compared to the GAP score (AUCs: 0.66-0.75).
• Six high-risk signature genes (GASK1B, HRK1, HTRA1, KCNN4, MMP9, SPP1) associated with cold exposure in IPF were identified.

Conclusions:

• Cold exposure is a potential environmental factor contributing to IPF progression.
• The developed prognostic model effectively assesses IPF patient severity.
• Identified signature genes may serve as novel biomarkers and therapeutic targets for IPF.