Identification of novel biomarkers and small molecule drugs in human colorectal cancer by microarray and bioinformatics analysis.

BACKGROUND

Colorectal cancer (CRC) is one of the most common malignant tumors. In the present study, the expression profile of human multistage colorectal mucosa tissues, including healthy, adenoma, and adenocarcinoma samples was downloaded to identify critical genes and potential drugs in CRC.

METHODS

Expression profiles, GSE33113 and GSE44076, were integrated using bioinformatics methods. Differentially expressed genes (DEGs) were analyzed by R language. Functional enrichment analyses of the DEGs were performed using the Database for Annotation, visualization, and integrated discovery (DAVID) database. Then, the search tool for the retrieval of interacting genes (STRING) database and Cytoscape were used to construct a protein-protein interaction (PPI) network and identify hub genes. Subsequently, survival analysis was performed among the key genes using Gene Expression Profiling Interactive Analysis (GEPIA). Connectivity Map (CMap) was used to query potential drugs for CRC.

RESULTS

A total of 428 upregulated genes and 751 downregulated genes in CRC were identified. The functional changes of these DEGs were mainly associated with cell cycle, oocyte meiosis, DNA replication, p53 signaling pathway, and progesterone-mediated oocyte maturation. A PPI network was identified by STRING with 482 nodes and 2,368 edges. Survival analysis revealed that high mRNA expression of AURKA, CCNB1, CCNF, and EXO1 was significantly associated with longer overall survival. Moreover, CMap predicted a panel of small molecules as possible adjuvant drugs to treat CRC.

CONCLUSION

Our study found key dysregulated genes involved in CRC and potential drugs to combat it, which may provide novel insights and potential biomarkers for prognosis, as well as providing new CRC treatments.