Prediction And Verification Of Core Genes In Colorectal Cancer By Bioinformatics

Background:Colorectal cancer is the third most prevalent cancer in the world,with the second highest mortality among all cancers.By 2030,the global burden of colorectal cancer is expected to increase by 60%,with more than 2.2 million new cases and 1.1 million deaths.The early symptoms of colorectal cancer are atypical and often missed or misdiagnosed.Colorectal cancer is usually found in the middle and late stages of the disease.The common early detection methods of colorectal cancer include fecal examination,blood examination and enteroscopy.However,several instrument related detection methods may not be available in areas with limited economic resources.The main treatment options for colorectal cancer are surgery,neoadjuvant radiotherapy(rectal cancer),adjuvant chemotherapy(stage III / IV and high-risk stage II colorectal cancer),and molecular targeted drug therapy.However,these treatments have some disadvantages.Therefore,it is very important to identify new biomarkers to understand the molecular changes driving colorectal cancer for early diagnosis and new target therapy.ObjectiveTo explore the pathogenesis of colorectal cancer through a bioinformatic approach to provide evidence for the prevention and treatment of colorectal cancerMethodsThe differentially expressed genes(DEGs)in colon cancer and normal colon mucosa in GSE110224、GSE113513、GSE126092 dataset were analyzed using GEO2 R online tool.GO analysis and KEGG pathway enrichment analysis of the DEGs in DAVID database were performed.The protein interaction network was constructed using STRING database,and the key genes(Hub genes)were screened and their functional modules were analyzed using Cytoscape software.The GEPIA database was used to validate the Hub genes,and the Target Scan database was used to predict the micro RNAs that regulate the target genes;OncomiR was used to analyze the expressions of the micro RNAs in colon cancer tissues and their relationship with the survival outcomes of the patients.GSE110224,GSE 113513 and GSE 126092(with | logfc | > 1 and P < 0.05)were screened out 1236,2919 and 2659 genes differentially expressed in colorectal cancer and adjacent tissues respectively.The intersection of GSE 110224,GSE 113513 and GSE 126092 genes was found by drawing Venn diagram,There are 139 up-regulated genes and 95 down regulated genes.Among them,139 up-regulated genes were mainly involved in cell adhesion / cell response to hypoxia,positive regulation of transforming growth factor β receptor signaling pathway,PI3 K Akt signaling pathway,transcription disorders in cancer,MAPK signaling pathway and other processes.The functional analysis of 95 down regulated genes showed that they were mainly enriched in the following biological processes: collagen catabolism,cell proliferation,G2 / M transformation of mitotic cell cycle,p53 signaling pathway,cytokine cytokine receptor interaction.".59(24 up-regulated genes,35 down-regulated genes)hub genes were screened by protein interaction network.GEPIA database showed that 10 genes(SCG2、NR3C2、AURKA、CCNA2、CCNB1、CHRDL1、CLCA1、COL8A1、CXCL2、ZG16)were related to the poor prognosis of colorectal cancer patients.Three genes((SCG2,CCNB1,CCNA2)are related to the stage of colorectal cancer,and they are related in colorectal cancer.Mir-802 binds to 3’UTR of(SCG2 m RNA.Compared with normal tissues,mir-802 was down-regulated in colorectal cancer tissues,and was associated with poor prognosis in colorectal cancer patients.ConclusionWe determined the core genes SCG2、NR3C2、AURKA、CCNA2、CCNB1、CHRDL1、CLCA1、COL8A1 、 CXCL2 and ZG16 related to the proliferation and prognosis of colorectal cancer by Bioinformatics Method;SCG2 may interact with CCNB1 and CCNA2 to influence the progress of colorectal cancer;further research results show that miR-802 can inhibit the proliferation and progress of colorectal cancer by targeting SCG2.Our findings increase our understanding of the molecular mechanism of colorectal cancer development,and may contribute to the development of early diagnosis and targeting of colorectal cancer.