Integrated Bioinformatics Analysis and Experimental Verification of Immune Cell Infiltration and the Related Core Genes in Ulcerative Colitis.

IF 1.8 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pharmacogenomics & Personalized Medicine Pub Date : 2023-01-01 DOI:10.2147/PGPM.S406644
Danya Zhao, Danping Qin, Liming Yin, Qiang Yang
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Abstract

Background: Ulcerative colitis is a recurrent autoimmune disease. At present, the pathogenesis of UC is not completely clear. Hence, the etiology and underlying molecular mechanism need to be further investigated.

Methods: Three sets of microarray datasets were included from the Gene Expression Omnibus database. The differentially expressed genes in two sets of datasets were analyzed using the R software, and the core genes of UC were screened using machine learning. The sensitivity and specificity of the core genes were evaluated with the receiver operating characteristic curve in another microarray dataset. Subsequently, the CIBERSORT tool was used to analyze the relationship between UC and its core genes and immune cell infiltration. To verify the relationship between UC and core genes and the relationship between core genes and immune cell infiltration in vivo.

Results: A total of 36 DEGs were identified. AQP8, HMGCS2, and VNN1 were determined to be the core genes of UC. These genes had high sensitivity and specificity in receiver operating characteristic curve analysis. According to the analysis of immune cell infiltration, neutrophils, monocytes, and macrophages were positively correlated with UC. AQP8, HMGCS2, and VNN1 were also correlated with immune cell infiltration to varying degrees. In vivo experiments verified that the expressions of neutrophils, monocytes, and macrophages increased in the UC colon. Furthermore, the expressions of AQP8 and HMGCS2 decreased, whereas that of VNN1 increased. Azathioprine treatment improved all the indicators to different degrees.

Conclusion: AQP8, HMGCS2, and VNN1 are the core genes of UC and exhibit different degrees of correlation with immune cells. These genes are expected to become new therapeutic targets for UC. Moreover, the occurrence and development of UC are influenced by immune cell infiltration.

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溃疡性结肠炎免疫细胞浸润及相关核心基因的综合生物信息学分析与实验验证。
背景:溃疡性结肠炎是一种复发性自身免疫性疾病。目前,UC的发病机制尚不完全清楚。因此,病因和潜在的分子机制需要进一步研究。方法:从Gene Expression Omnibus数据库中获取三组微阵列数据集。使用R软件分析两组数据集中的差异表达基因,并使用机器学习筛选UC的核心基因。核心基因的敏感性和特异性用另一个微阵列数据集的接收器工作特征曲线进行评估。随后,利用CIBERSORT工具分析UC及其核心基因与免疫细胞浸润的关系。验证UC与核心基因的关系以及核心基因与体内免疫细胞浸润的关系。结果:共鉴定出36个deg。AQP8、HMGCS2和VNN1是UC的核心基因。这些基因在受试者工作特性曲线分析中具有较高的敏感性和特异性。免疫细胞浸润分析发现,中性粒细胞、单核细胞和巨噬细胞与UC呈正相关。AQP8、HMGCS2、VNN1也与免疫细胞浸润有不同程度的相关性。体内实验证实,UC结肠中中性粒细胞、单核细胞和巨噬细胞的表达增加。AQP8和HMGCS2表达降低,VNN1表达升高。硫唑嘌呤处理对各指标均有不同程度的改善。结论:AQP8、HMGCS2、VNN1是UC的核心基因,与免疫细胞有不同程度的相关性。这些基因有望成为UC的新的治疗靶点。此外,UC的发生发展受免疫细胞浸润的影响。
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来源期刊
Pharmacogenomics & Personalized Medicine
Pharmacogenomics & Personalized Medicine Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
3.30
自引率
5.30%
发文量
110
审稿时长
16 weeks
期刊介绍: Pharmacogenomics and Personalized Medicine is an international, peer-reviewed, open-access journal characterizing the influence of genotype on pharmacology leading to the development of personalized treatment programs and individualized drug selection for improved safety, efficacy and sustainability. In particular, emphasis will be given to: Genomic and proteomic profiling Genetics and drug metabolism Targeted drug identification and discovery Optimizing drug selection & dosage based on patient''s genetic profile Drug related morbidity & mortality intervention Advanced disease screening and targeted therapeutic intervention Genetic based vaccine development Patient satisfaction and preference Health economic evaluations Practical and organizational issues in the development and implementation of personalized medicine programs.
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