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基于生物信息学的结直肠癌枢纽基因与预后相关基因筛选

Objective

To screen differentially expressed genes (DEGs) between colorectal cancer and normal colorectal mucosa tissues by bioinformatics and analyze their relationship with prognosis.

Methods

Colorectal cancer gene microarrays datasets GSE110224, GSE41328 and GSE22598 were downloaded from Gene Expression Omnibus (GEO) database. DEGs between colorectal cancer samples and normal tissue samples from those three datasets were screened by R software 4.0.3, and then GO and KEGG pathway analysis were carried out. The protein interaction network was constructed by STRING database, Cytoscape software v3.7.2 was used to screen the hub genes in the protein-protein interaction (PPI) network. Finally, the selected hub genes were validated and analyzed for the relationship with prognosis by the GEPIA database.

Results

A total of 366 DEGs were screened, of which 128 were up-regulated and 238 were down-regulated. GO function enrichment showed hub genes were mainly involved in proteolysis, positive regulation of proliferation and other biological processes, and cellular component mainly enriched in extracellular space, extracellular region, mediating zinc ion binding, calcium ion binding and other molecular functions. KEGG analysis showed that the enriched pathways are mainly related to cytokine-cytokine receptor interaction, chemokine signaling pathway and other signal transduction pathway. Ten hub genes were selected from the PPI network, including nine up-regulated genes, which were CXCL8, CXCL1, SPP1, COL1A1, SOX9, MMP3, COL1A2, CD44, CXCL5, and one down-regulated gene CXCL12. Those ten genes were verified by using GEPIA showing that eight of them existed significant difference and all of them were consistent with the above analysis. Survival analysis results showed that genes CXCL8, SPP1 and COL1A2 were significantly associated with the survival rate of colorectal tumor patients.

Conclusion

CXCL8 and SPP1 may be prognosis key genes of colorectal tumor patients and may serve as a potential biomarker providing basis on molecular level for screening and diagnosis of colorectal tumor.

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