C-X-C Motif Chemokine 12 Was Identified as a Potential Gene Target in the Treatment of Crohn's Disease.

Abstract

Object: The present study aimed to identify hub genes associated with the treatment and control of active and inactive Crohn's disease (CD).

Methods: Differentially expressed genes (DEGs) were identified in normal, active CD, and inactive CD samples from GSE95095 dataset. Intersection genes screened by Venn diagram in DEGs. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted on the intersection genes. The protein-protein interaction (PPI) network was used to screen of hub gene. The expression and mRNA levels of CXCL12 in CD and ROC curves in GSE95095 dataset. Signaling pathways of hub genes and their correlation with immune cells were analyzed by gene set enrichment analysis (GSEA), EPIC, and ESTIMATE, respectively. Finally, immunohistochemistry (IHC) and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) were used to detect the expression of the hub gene in normal, inactive, and active CD tissues.

Results: In GSE95095 dataset, CXCL12 was identified as the most hub gene by limma analysis, Venn diagram and A protein-protein interaction (PPI) network. CXCL12 expression was highest in active CD (p < 0.001) followed by inactive CD (p < 0.01). Subsequently, it was validated through IHC and RT-PCR in normal intestinal mucosal, active CD, and inactive CD. CXCL12 was overexpressed in active and inactive CD (IHC: p < 0.001 and RT-PCR: p < 0.001, respectively). CXCL12 expression in active CD was determined via analysis with receiver operating characteristic (ROC) curves. The specificity and sensitivity were 0.875 and 0.625, respectively, the accuracy was 72.92%, the area under the curve (AUC) was 0.780, and the 95% confidence interval (CI) was in the range of 0.648-0.912. CXCL12 expression was closely correlated with various immune cells.

Conclusion: CXCL12 is overexpressed in active CD and is closely correlated with various immune cells. We propose that CXCL12 as a potential target genes for the treatment and management of both active and inactive CD.