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

Abstract

BackgroundAlthough 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.MethodsThe 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.ResultsA 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.ConclusionOur 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.

Bioinformatics Prediction for Network-Based Integrative Multi-Omics Expression Data Analysis in Hirschsprung Disease

“…The use of this second previously reported method, validated for IBD, is suitable for isolating miRNAs for similar types of diseases [57]. Although HSCR was not identified in its miRNA-disease network, as we mentioned above, the co-occurrence of IBD, especially Crohn's disease, has been recently reported in children with HSCR [133,134], and common pathogenesis and hub gene biomarkers have been also identified [143].…”

Determining the link between psoriasis and Crohn's disease using bioinformatics and systems biology approaches

“…The dataset GSE114286 18 contains total RNA sequences from 9 healthy volunteers and 18 patients with psoriasis vulgaris. The dataset GSE95095 19 comprises 24 samples from individuals with Crohn's disease (CD) and 12 samples from healthy controls (Table S1). It is important to note that all test specimens were obtained from humans.…”