肠息肉与早期结直肠癌基因表达谱特征差异的生物信息学分析

Bioinformatics Analysis of Gene Expression Profile Differences Between Intestinal Polyps and Early Colorectal Cancer

目的应用生物信息学方法研究从肠息肉发展成为结肠癌的关键分子标志物,筛选出与早期CRC发生、发展相关的基因。研究由肠息肉向结直肠癌的转变机制,为CRC发生发展的机制提供线索和思路。方法从公共基因表达数据库(GEO)下载CRC基因芯片GSE8671、GSE9348数据集,采用R4.1.1软件和Rstudio进行数据处理和分析。利用limma包分别筛选出肠息肉与正常组织、早期结直肠癌和正常组织间差异表达的基因(DEGs),Venn分析对肠息肉和结直肠癌的DEGs进行筛选。并对DEGs进行GO和KEGG富集分析,筛选出由肠息肉转变为结直肠癌的关键分子标志物。结果初步筛选出了CDH3、CXCL8、CEMIP、DPEP1、MMP3等在腺瘤中下调,而在早期CRC中表达上调的关键基因。GO富集分析显示,阴离子跨膜转运途径在早期结直肠癌的发生发展中起着重要的作用。KEGG富集分析显示IL-17信号转导通路,TNF信号通路和视黄醇代谢等通路可能在腺瘤向早期结直肠癌的发展过程中发挥作用。结论通过基因芯片结合生物信息学方法发现了与早期结直肠癌相关的5个关键基因,包括CDH3、CXCL8、CEMIP、DPEP1、MMP3,对肠息肉向肠癌的转变机制研究以及结直肠癌的早期诊断具有重要的意义。

Objective To study the key molecular markers from intestinal polyps to colon cancer by bioinformatics methods,and to screen out the genes related to the occurrence and development of early CRC.Meanwhile to study the mechanism of the transformation from intestinal polyps to colorectal cancer,and to provide clues and ideas for the mechanism of CRC development.Methods The CRC gene chip GSE8671 and GSE9348datasets were downloaded from the public gene expression database(GEO).R4.1.1 software and Rstudio were used for data processing and analysis.The differentially expressed genes(DEGs)between intestinal polyps and normal tissues,early colorectal cancer and normal tissues were screened by limma package,and the DEGs of intestinal polyps and colorectal cancer were screened by Venn analysis.GO and KEGG enrichment analysis were performed on DEGs to screen out the key molecular markers for the transformation from intestinal polyps to colorectal cancer.Results The key genes such as CDH3,CXCL8,CEMIP,DPEP1 and MMP3 were down-regulated in adenoma and up-regulated in early CRC.GO enrichment analysis showed that the anion transmembrane transport pathway played an important role in the development of early colorectal cancer.KEGG enrichment analysis showed that IL-17 signal transduction pathway,TNF signaling pathway and retinol metabolism pathway may play a role in the development of adenoma to early colorectal cancer.Conclusion Five key genes associated with early colorectal cancer,including CDH3,CXCL8,CEMIP,DPEP1 and MMP3,are identified by gene microarray combined with bioinformatics method,which is of great significance for the study of the transformation mechanism of intestinal polyps to colorectal cancer and the early diagnosis of colorectal cancer.