Identification of hub programmed cell death-related genes and immune infiltration in Crohn's disease using bioinformatics

Biyao Wang; Hailing Liu; Qin Guo; Xiang Gao; Kang Chao; Qingfan Yang

doi:10.3389/fgene.2024.1425062

Identification of hub programmed cell death-related genes and immune infiltration in Crohn's disease using bioinformatics

Front Genet. 2024 Dec 18:15:1425062. doi: 10.3389/fgene.2024.1425062. eCollection 2024.

Authors

Biyao Wang^#^{1

2}, Hailing Liu^#^{3

4}, Qin Guo^{1

2}, Xiang Gao^{1

5}, Kang Chao^{1

5}, Qingfan Yang^{1

4}

Affiliations

¹ Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
² Department of Small Bowel Endoscopy, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
³ Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
⁴ Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
⁵ Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

^# Contributed equally.

Abstract

Background: Crohn's disease (CD) is an immune-mediated disorder characterized by immune cell infiltration that induces persistent chronic inflammation of the gastrointestinal tract. Programmed cell death (PCD) plays a critical role in the pathogenesis of CD. This study identified vital PCD-related genes in CD based on immune infiltration using bioinformatic analysis.

Methods: We obtained two CD datasets from the Gene Expression Omnibus (GEO) database and examined immune cell infiltration to investigate immune cell dysregulation in CD. PCD-related genes were retrieved from the GeneCards database. Based on the differentially expressed genes (DEGs) and PCD gene sets, PCD-related DEGs were identified. Candidate hub genes were identified using a protein-protein interaction (PPI) network, and their diagnostic effectiveness was predicted using receiver operating characteristic (ROC) curve analysis. Functional enrichment and immune infiltration analyses were used to assess the distinct roles of the hub genes. Finally, the miRWalk and ENCORI databases were used to predict which microRNAs (miRNAs) regulated the hub genes and to verify gene expression in CD colonic tissues via transcriptome sequencing.

Results: A total of 335 PCD-related DEGs and 3 hub genes (MMP1, SAA1, and PLAU) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses indicated the enrichment of these genes in the immune response. Infiltration analysis of immune cells showed abundant endothelial cells, plasma cells, dendritic cells, and monocytes in the CD samples. Based on the correlation analysis, the three hub genes were positively correlated with monocytes and negatively correlated with CD8 naïve T-cells. MMP1, SAA1, and PLAU correlated with the pathogenicity of CD and had good diagnostic value for CD. The three hub genes were highly expressed in the CD tissues, as confirmed using transcriptome sequencing.

Conclusion: This study identified MMP1, SAA1, and PLAU as hub genes involved in PCD in patients with CD. These genes regulate immune cell function and their expression levels are closely related to immune cell infiltration. These findings provide novel insights into the mechanisms underlying CD pathogenesis. The identified PCD genes and regulatory miRNAs are potential biomarkers and therapeutic targets for CD.

Keywords: Crohn’s disease; bioinformatics; functional enrichment analysis; immune infiltration; programmed cell death.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was supported by the Guangdong Provincial Clinical Research Center for Digestive Diseases (No. 2020B1111170004) and Guangzhou Science and Technology Plan Project (No. 2024A04J4324).