Jianghao Wang, Meiyi You, Jichang Li, Xin Wang, Yucun Liu, Shanwen Chen, Pengyuan Wang

Department of Gastrointestinal Surgery, Peking University First Hospital, Peking University, Beijing, 100034, People’s Republic of China

Correspondence: Pengyuan Wang, Email pengyuan_wang@bjmu.edu.cn Shanwen Chen, Email shanwen@pku.edu.cn

Objective: This study investigated the correlation between circadian rhythm genes and ulcerative colitis (UC), aiming to identify biomarkers linked to immune microenvironment changes in UC.
Methods: Gene expression data from UC patients and healthy controls were obtained from the GEO database. Data preprocessing included batch correction and PCA for consistency assessment. Differentially expressed genes (DEGs) were identified using the “limma” package, and functional enrichment analysis was performed. Machine learning methods (LASSO, SVM, RF) refined candidate biomarkers. RNA sequencing in a mouse colitis model and immune infiltration analysis validated key genes. A regulatory network of lncRNA, miRNA, and mRNA for hub genes was constructed.
Results: 805 DEGs were identified, including 15 rhythm genes. Four key genes (CPT1A, PRKG2, PPARGC1A, SLC6A4) were screened, with PPARGC1A and SLC6A4 validated as hub genes. These genes were associated with immune cell infiltration and hold potential as biomarkers for UC diagnosis.
Conclusion: Disruptions in circadian rhythm are closely associated with the pathogenesis of ulcerative colitis (UC). The biomarkers PPARGC1A and SLC6A4 demonstrated significantly altered expression in UC patients and were correlated with immune cell infiltration. These findings underscore their potential as diagnostic markers, provide new insights into the immune microenvironment and pathogenesis of UC, and suggest potential therapeutic targets for the disease.

Keywords: ulcerative colitis, circadian rhythm genes, PPARGC1A, SLC6A4