A prognostic model of idiopathic pulmonary fibrosis constructed based on macrophage and mitochondria-related genes
Yu Bao1, Shiyuan Yang1, Hailan Zhao1
1First School of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Shandong, China.
Background:
Studies have shown that mitochondrial function and macrophages may play a role in the development of idiopathic pulmonary fibrosis (IPF). However, the understanding of the interactions and specific mechanisms between mitochondrial function and macrophages in pulmonary fibrosis is still very limited.
Methods:
To construct a prognostic model for IPF based on Macrophage- related genes (MaRGs) and Mitochondria-related genes (MitoRGs), differential analysis was performed to achieve differentially expressed genes (DEGs) between IPF and Control groups in the GSE28042 dataset. Then, MitoRGs, MaRGs and DEGs were overlapped to screen out the signature genes. The univariate Cox analysis and the least absolute shrinkage and selection operator (LASSO) algorithm were implemented to achieve key genes. Furthermore, the independent prognostic analysis was employed. The ingenuity pathway analysis (IPA) was employed to further understand the molecular mechanisms of key genes.Next, the immune infiltration analysis was implemented to identify differential immune cells between two risk subgroups.
Results:
There were 4791 DEGs between IPF and Control groups. Furthermore, 26 signature genes were achieved by the intersection processing. Three key genes including ALDH2, MCL1, and BCL2A1 were achieved, and the risk model based on the key genes was created. In addition, a nomogram for survival forecasting of IPF patients was created based on riskScore, Age, and Gender, and we found that key genes were associated with classical pathways including 'Apoptosis Signaling', 'PI3K/AKT Signaling', and so on. Next, two differential immune cells including Monocytes and CD8 T cells were identified between two risk subgroups. Moreover, we found that MIR29B2CHG and hsa-mir-1-3p could regulate the expression of ALDH2.
Conclusion:
We achieved 3 key genes including ALDH2, MCL1,, and BCL2A1 associated with IPF, providing a new theoretical basis for clinical treatment of IPF.
Insights
This study identifies three key genes—ALDH2, MCL1, and BCL2A1—involved in idiopathic pulmonary fibrosis (IPF) by analyzing macrophage and mitochondrial gene interactions. These findings offer a new foundation for IPF clinical treatment strategies.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Genetics
Background:
- Mitochondrial dysfunction and macrophage activity are implicated in idiopathic pulmonary fibrosis (IPF).
- The precise mechanisms linking mitochondrial function and macrophages in IPF remain poorly understood.
Purpose of the Study:
- To develop a prognostic model for IPF utilizing macrophage-related genes (MaRGs) and mitochondria-related genes (MitoRGs).
- To identify key genes and molecular pathways associated with IPF prognosis and immune cell infiltration.
Main Methods:
- Differential gene expression analysis was conducted on the GSE28042 dataset to identify differentially expressed genes (DEGs) between IPF and control groups.
- Signature genes were identified by overlapping DEGs with MaRGs and MitoRGs, followed by univariate Cox analysis and LASSO regression to pinpoint key prognostic genes.
- Ingenuity pathway analysis (IPA) and immune infiltration analysis were performed to explore molecular mechanisms and differential immune cell populations.
Main Results:
- 4791 DEGs were identified; 26 signature genes were selected, leading to the identification of three key genes: ALDH2, MCL1, and BCL2A1.
- A prognostic risk model and a nomogram incorporating risk score, age, and gender were developed for IPF patient survival forecasting.
- Key genes were linked to 'Apoptosis Signaling' and 'PI3K/AKT Signaling' pathways; Monocytes and CD8 T cells were identified as differential immune cells between risk subgroups. MIR29B2CHG and hsa-mir-1-3p were found to regulate ALDH2 expression.
Conclusions:
- Three key genes (ALDH2, MCL1, BCL2A1) associated with IPF were identified, offering a novel theoretical basis for clinical interventions.
- The study provides insights into the complex interplay between mitochondrial function, macrophages, and IPF pathogenesis.
- The developed prognostic model and identified pathways may aid in predicting IPF progression and guiding therapeutic strategies.
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