Page 6 - 北京京煤集团总医院第十一届·2023学术年会论文集

北京京煤集团总医院 第十一届·2023 学术年会论文集

in epigenetics; they are mainly involved in DNA methylation, histone modification, chromatin
remodeling, and the production of miRNAs that affect protein concentrations in the cell [9] .

Defective chromatin regulation is associated with the development of multiple diseases [10] .
Corticosteroids have been among the main modalities for the treatment of asthma, but possible
reasons for their inefficacy in severe asthma are the failure to recruit HDAC2/SIRT1 and the
presence of oxidatively/post-translationally modified HDAC2/SIRT1 in asthmatics [11] . Epigenetic

markers regulate many processes in T lymphocytes in asthma. Furthermore, the identification of
DNA methylation of specific nucleotides as biomarkers of asthma has been previously reported [12] .
However, an in-depth study on the role of CRs in severe asthma is important for the treatment and
prognosis of this condition.

In this study, we analyzed previously determined gene expression and clinical data of patients
with severe asthma and healthy individuals. We also sorted the genes encoding CRs based on
information from previous literature. The comprehensive analysis of the data was expected to
provide new insights into the treatment and prognosis of severe asthma.

2. Materials and methods
2.1 Data collection and preprocessing
Information from accession GSE143303 was downloaded from the Gene Expression Omnibus

(GEO) database [13] of the National Center for Biotechnology Information (NCBI); it includes
transcriptome data from endobronchial biopsy samples of 47 patients with severe asthma and 13
healthy participants [14] . In addition, we curated information from 870 CRs from the published
literature [15]. RStudio (version 1.4.1717.0) was used to normalize the gene expression profile of

GSE143303. Subsequently, expression matrices of CRs in patients with severe asthma were
obtained [16] . The limma package was used to identify differentially expressed CRs according to the
following criteria: |log fold change (FC)| ≥ 0.2 and P < 0.05.
Patients with severe asthma included in this study were defined as those treated for GINA step

4 or 5, requiring high doses of inhaled corticosteroids (ICS) and a second “controller” after which
the condition remained uncontrolled and either had persistent symptoms and/or worsened.
Specifically, the high dose of ICS refers to >500 μg fluticasone or equivalent per day [6, 17] . Clinical
characteristics of patients with severe asthma and healthy controls have been presented in a

previously published article [17] .
2.2 Enrichment analysis of differentially expressed CRs
To understand the potential function of the differentially expressed CRs, Gene Ontology (GO)

analysis, including the GO terms molecular function (MF), biological process (BP), and cellular
component (CC)), was performed using the aclusterProfiler R package. A Kyoto Encyclopedia of
Genes and Genomes (KEGG) pathway-based analysis was also performed. Enrichment results were
visualized using the enrichplot package.
2.3 Construction a protein to protein interaction (PPI) network

Using STRING, a PPI network of differentially expressed CRs was constructed [18] . The top 10

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