Identification of Ulcerative Colitis Biomarkers and Potential Small Molecule Drug Screening Based on Immunosignature Genes of Recurrent Aphthous Ulcers

CAO Shuqing; CHEN Meng; HU Peiting; JIAO Boheng; ZHANG Yujing

doi:10.13730/j.issn.2097-2148.2024.04.008

Abstract：Objective To explore the clinical significance of immunosignature genes of recurrent aphthous ulcers(RAU)in ulcerative colitis(UC)through bioinformatics multi-chip joint analysis and machine learning techniques.Meth-ods Transcriptome data of RAU and UC were downloaded from the Gene Expression Omnibus(GEO)database,and a list of immune-related genes was obtained from the Immunology Database and Analysis Portal(IMMPORT).Weighted gene co-expression network analysis(WGCNA),differential analysis and functional enrichment analysis were used to screen and evaluate RAU disease genes and its functions,the RAU immunosignature genes were screened by LASSO-Cox regression and random forest.The expression levels of RAU immunosignature genes in UC samples were validated and subjected to Friends analysis,the diagnostic efficiency of these genes was identified by a multi-layer perception(MLP)artificial neural network.Based on im-munosignature genes,a consistency clustering algorithm was employed to classify UC samples molecularly,explo-ring different subtypes'levels of immune cell infiltration and biological features.Finally,targeted drug screening was per-formed by the Integrated Traditional Chinese Medicine(ITCM),and molecular docking validation and simulated pharma-cokinetic analysis were conducted by CB-dock2 and SwissADME platforms.Results A total of 324 disease genes related to RAU were identified.Functional enrichment analysis indicated that RAU disease genes were mainly associated with risk factors like immune inflammation,microbial infections and inflammatory bowel disease etc.Further screening,vali-dating and identifying defensin beta 4A(DEFB4A),bone marrow stromal cell antigen 2(BST2),thymidine phosphoryl-ase(TYMP)and glia maturation factor gamma(GMFG)as highly expressed immune characteristic genes,which demon-strating diagnostic value for UC[area under the curve(AUC)=0.915].RAU and UC shared a common T-cell disorder foundation,immunosignature genes could differentiate UC into metabolic and immune subtypes,with the immune subtype exhibiting higher expression of signature genes and levels of T-cell subset infiltration.Ten natural small molecule drugs were screened,and molecular docking showed good binding activity with the translation proteins of immune characteristic genes,moreover,hupehenine demonstrated favorable pharmacokinetic parameters,which might become potential UC therapeutic drugs.Conclusion Immunosignature genes based on RAU can effectively differentiate UC samples and identi-fy subtypes,which providing a theoretical basis and new perspectives for basic research on digestive inflammatory disea-ses,clinical disease auxiliary screening,potential preventive and therapeutic drug screening.