Screening Of Key Genes Involved In The Transformation Of Ulcerative Colitis To Colon Cancer And The Prediction Of Potential Traditional Chinese Medicines

Objective :Ulcerative Colitis(UC)is one of the risk factors for Colon Cancer(CC),and the chronic inflammatory environment can accelerate the progression of UC,and increase the risk of CC.In this paper,we used the GEO database and bioinformatics technology to screen the differential genes transformed from UC to CC.Subsequently,we analyzed the key genes and explored their expression levels and mutations.We have predicted potential traditional Chinese medicine related to the transformation of ulcerative colitis into colon cancer,explored the potential components of traditional Chinese medicine and their regulatory target gene mechanisms.It provides a theoretical basis for future Chinese medicine treatment of UC to CC transformation.Methods : 1.The GEO chip database was used to download datasets GSE87473,GSE44076 and GSE37283.The experimental platforms of the datasets GSE87473 and GSE37283 were GPL13158,and GSE87473 had a total of 127 samples,including106 UC samples and 21 normal samples;GSE37283 contains 20 samples,including 4UC samples,11 UC with CRC samples and 5 normal samples.The GSE44076 chip dataset is based on GPL13667,with a t otal of 246 samples,including 98 CC and 148 normal and paracancerous samples.The GEO online tool GEO2 R combined with venny2.1.0 was used to screen Differential Expressed Genes(DEGs).2.The DAVID database combined with R software was used to perform GO function analysis and KEGG pathway enrichment analysis of the differentially expressed associated candidate genes of UC and CC.3.Using the STRING 11.5 database combined with Cytoscape 3.9.1 software to obtain the Protein Protein Interaction(PPI)network diagram,and using the Cyto Hubba plug-in to obtain key genes.4.Graph Pad Prism 9.5 software was used to verify whether there was a statistical difference in the expression of key genes in the validation set of UC and CC.5.Mutation analysis of key genes to understand gene mutations.6.10 key genes were entered into the medical ontology information retrieval platform(Coremine Medical)to map out potential traditional Chinese medicines.TCMSP and Uniprot database were used to jointly obtain traditional Chinese medicine ingredients and targets,imported into Cytoscape software to construct a "traditional Chinese medicine-active ingredient-target" action network diagram.And the top 25 target genes in the network map were screened using Cyto Hubba plugin.Results: 1.UC chip and CC chip GSE87473,GSE44076 and GSE37283 were downloaded from GEO database.A total of 140 intersection difference genes were obtained,including 68 upregulated genes and 72 downregulated genes.2.Gene Ontology functional analysis showed that UC-CC-related candidate genes were mainly enriched in biological processes such as inflammatory response,overall membrane composition,and cytokine activity.KEGG pathway enrichment analysis showed that UC-CC-related candidate genes were mainly enriched in IL-17 signaling pathway and TNF signaling pathway.3.PPI network diagram was constructed using STRING database and Cytoscape software.The node genes in the network diagram were ranked by Degree,and the top10 genes were considered as key genes.4.The above key genes were verified,and it was found that the 10 key genes were statistically different(P < 0.05).Finally it was concluded that the following 10 genes MPP1、TIMP1、TLR2、MMP3、MMP9、CXCL1、CD44、SPP1、IL1B and LCN2 may be related to the transformation process of ulcerative colitis to colon cancer,and their expressions are all up-regulated.5.The representative drugs of traditional Chinese medicines screened include panax notoginseng,scutellaria baicalensis,ginseng leaf and angelica,which regulate PTGS2,PTGS1,NOCA2 and other targets through active ingredients such as quercetin,legustarol,β-sitosterol and kaempferol,which may affect the transformation process of UC-CC.Conclusions:MPP1,TIMP1,TLR2,MMP3,MMP9,CXCL1,CD44,SPP1,IL1 B and LCN2 are key genes in the transformation of UC into CC.It was predicted that four traditional Chinese medicines,including Panax notoginseng,Scutellaria baicalensis,ginseng leaf and angelica,could intervene in the transformation of UCto CC through active ingredients such as quercetin,legustarol,β-sitosterol and kaempferol by regulating PTGS2,PTGS1,NOCA2 and other targets.