Page 5 - 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

A prognosis prediction chromatin regulator signature for

patients with severe asthma

Running title: Chromatin regulators in severe asthma
Yaning Gao1*, Liang Chen1, Jian Li1, Zhengjun Wen1
1 Beijing Jingmei Group General Hospital, Beijing, China

* Correspondence: Yaning Gao,747808201@qq.com
Abstract:Severe asthma imposes a physical and economic burden on both patients and society. As
chromatin regulators (CRs) influence the progression of multiple diseases through epigenetic

mechanisms, we aimed to study the role of CRs in patients with severe asthma. Transcriptome data
(GSE143303) from 47 patients with severe asthma and 13 healthy participants was downloaded
from the Gene Expression Omnibus database. Enrichment analysis was performed to investigate the
functions of differentially expressed CRs between the groups. We identified 80 differentially

expressed CRs; they were mainly enriched in histone modification, chromatin organization, and
lysine degradation. A protein–protein interaction network was then constructed. The analyzed
immune scores were different between sick and healthy individuals. Thus, CRs with a high
correlation in the immune analysis, SMARCC1, SETD2, KMT2B, and CHD8, were used to construct

a nomogram model. Finally, using online prediction tools, we determined that lanatoside C,
cefepime, and methapyrilene may be potentially effective drugs in the treatment of severe asthma.
The nomogram constructed using the four CRs, SMARCC1, SETD2, KMT2B, and CHD8, may be a
useful tool for predicting the prognosis of patients with severe asthma. This study provided new

insights into the role of CRs in severe asthma.
Keywords: severe asthma, chromatin regulators, risk model, nomogram, epigenetics
1. Introduction
[1]
Currently, there are approximately 300 million patients with asthma worldwide . As a diffuse
respiratory disease, the main pathological features of asthma include airway inflammation and
[2]
remodeling, which result in airflow limitation and bronchial hyperresponsiveness . Standard
inhalation therapy is an effective means of controlling the condition of most asthmatic patients.
However, approximately 10% of the patients with asthma do not benefit from such therapies [3, 4] .

Patients with asthma who require high-dose inhaled corticosteroid treatments and a second
controller to prevent uncontrolled asthma attacks or who remain uncontrolled despite these
treatments are considered to have severe asthma [5]. The Global Initiative for Asthma (GINA)

recommends the corticosteroid, azithromycin, anti-IL4R, anti-thymic stromal lymphopoietin, long-
acting muscarine anticholinergic, short-acting -agonists, and anti-IgE antibody omalizumab for the
treatment of severe asthma [6] . However, as a heterogeneous disease, severe asthma requires
complex treatments .
[7]
Epigenetics refers to those modifications that alter chromatin and regulate gene expression
without altering the underlying DNA sequence . Chromatin regulators (CRs) are important factors
[8]

- 1 -