Shared Genes and Pathways in Ulcerative Colitis and Ankylosing Spondylitis: Functional Validation and Implications...

Area of Science:

• Immunology
• Genetics
• Gastroenterology

Background:

• Ulcerative colitis (UC) and ankylosing spondylitis (AS) share reported associations, but their common etiologies are not fully understood.
• Investigating shared genetic factors and mechanisms is crucial for understanding the relationship between UC and AS.

Purpose of the Study:

• To identify shared genes and elucidate relevant biological mechanisms in ulcerative colitis (UC) and ankylosing spondylitis (AS).
• To discover potential diagnostic biomarkers and therapeutic targets for both UC and AS.

Main Methods:

• Differential gene expression analysis was performed on UC and AS datasets (GSE113079, GSE1797879) to identify common differentially expressed genes (DEGs).
• Receiver operating characteristic (ROC) curve analysis, gene set enrichment analysis (GSEA), and immune infiltration analysis were employed to identify key genes and pathways.
• Reverse transcription-polymerase chain reaction (RT-PCR) was used to validate mRNA expression of key genes in patient samples.

Main Results:

• Eight key genes (GMFG, GNG11, CLEC4D, CMTM2, VAMP5, S100A8, S100A12, DGKQ) were identified as potential diagnostic biomarkers for AS and UC.
• Drugs including rimegepant, eptinezumab, methotrexate, atogepant, and ubrogepant were suggested as potential treatments targeting S100A12 and S100A8.
• GSEA revealed associations with antigen processing, natural killer cell cytotoxicity, and T cell receptor signaling pathways. Increased mRNA expression of S100A12, VAMP5, and CLEC4D was observed in patients.

Conclusions:

• The study identified key genes and shared pathways, enhancing the understanding of the relationship between UC and AS.
• These findings may inform the development of improved diagnostic and therapeutic strategies for patients with UC and AS.