Identification and validation of the common pathogenesis and hub biomarkers in Hirschsprung disease complicated with Crohn's disease

Jing Wang; Zejian Li; Jun Xiao; Luyao Wu; Ke Chen; Tianqi Zhu; Chenzhao Feng; Didi Zhuansun; Xinyao Meng; Jiexiong Feng

doi:10.3389/fimmu.2022.961217

Identification and validation of the common pathogenesis and hub biomarkers in Hirschsprung disease complicated with Crohn's disease

Front Immunol. 2022 Sep 28:13:961217. doi: 10.3389/fimmu.2022.961217. eCollection 2022.

Authors

Jing Wang^{1

2}, Zejian Li^{1

2}, Jun Xiao^{1

2}, Luyao Wu^{1

2}, Ke Chen^{1

2}, Tianqi Zhu^{1

2}, Chenzhao Feng¹, Didi Zhuansun^{1

2}, Xinyao Meng^{1

2}, Jiexiong Feng^{1

2}

Affiliations

¹ Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Hubei Clinical Center of Hirschsprung Disease and Allied Disorders, Wuhan, China.

Abstract

Background: Although increasing evidence has supported that Hirschsprung disease (HSCR) is the risk factor for children developing Crohn's disease (CD), the common mechanism of its co-occurrence remains unknown. The purpose of this study is to further explore the underlying mechanism and biomarkers for the co-occurrence of HSCR and CD.

Methods: The Gene Expression Omnibus (GEO) database was used to obtain gene expression profiles for CD (GSE95095) and HSCR (GSE98502). Following the identification of the shared differentially expressed genes (DEGs) of CD and HSCR, functional annotation, protein-protein interaction (PPI) network creation, and module assembly were performed to discover hub genes. RT-qPCR was performed to validate the expression of the hub genes in HSCR samples. The receiver operating characteristic (ROC) curve was utilized to assess the accuracy of the hub genes as biomarkers in predicting CD in both the training dataset and test dataset.

Results: A total of 103 common DEGs (50 downregulated genes and 53 upregulated genes) were chosen for further investigation. The importance of chemokines and cytokines in these two disorders is highlighted by functional analysis. MCODE plug identified three important modules, which functionally enriched the immune system process. Finally, nine hub genes were identified using cytoHubba, including IL1B, IL10, CXCL10, ICAM1, EGR1, FCGR3A, S100A12, S100A9, and FPR1. The nine hub genes were mainly enriched in immune- and inflammation-related pathways. External data profiles and RT-qPCR confirmed the expression of the nine hub genes in HSCR and CD. ROC analysis revealed that the nine hub genes had a strong diagnostic value.

Conclusion: Our study reveals the common pathogenesis of HSCR and CD. These hub genes and diagnostic models may provide novel insight for the diagnosis and treatment of HSCR complicated with CD.

Keywords: CXCL10; Crohn’s disease; Hirschsprung disease; diagnostic model; hub genes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers / metabolism
Child
Computational Biology
Crohn Disease* / complications
Crohn Disease* / genetics
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Hirschsprung Disease* / genetics
Humans
Interleukin-10 / metabolism
S100A12 Protein / genetics

Substances

Biomarkers
S100A12 Protein
Interleukin-10