Identification of Key Genes Involved in Colorectal Cancer: A Bioinformatics Analysis

Background: Colorectal cancer is the life-threatening tumor with the fourth highest incidence and fifth highest mortality worldwide, despite the unknown mechanism behind it. Methods: In this paper, the potential prognostic candidate biomarkers for colorectal cancer were tested by Bioinformatical analysis combined with the CRC clinical samples. It was from the gene expression omnibus (GEO) that three datasets (GSE32323, GSE44076 and GSE43078) were collected. With the limma and clusterProfifiler packages applied, the differentially expressed genes (DEGs) were identified and functional enrichment analysis was conducted. The Search Tool intended for the Retrieval of Interacting Genes (STRING) database was employed to construct a protein–protein interaction (PPI) network, while the module analysis was carried out using Cytoscape. Subsequently, the online tool The Gene Expression Profiling Interactive Analysis (GEPIA; http://gepia.cancer-pku.cn/index.html) was applied to conduct overall survival analysis, while prognostic candidate biomarkers were subject to a further analysis through the Oncomine database. Ultimately, 4 critical hub genes were chosen and validated for their expression among 9 patients with CRC diagnosis by means of reverse transcription-quantitative PCR (RT-qPCR). To evaluate the accuracy of prediction, time-dependent receiver operating characteristic (ROC) was applied. Outcomes: In total, 547 DEGs were identified, inclusive of 475 downregulated and 72 upregulated genes which underwent significant enrichment over the course of cellular response to hypoxia, Positive regulation of ERK1 and ERK2 cascade and Positive regulation of apoptotic process. The major pathways with enrichment were Pathways in cancer,PI3K-Akt signaling pathway,cGMP-PKG signaling pathway. After the extraction of critical modules from the PPI network, 10 hub genes were removed. These 10 hub genes are all up-regulated genes and are highly expressed in colorectal cancer. Survival analysis shows that only CCNB1 and CCNA2 are associated with the survival prognosis of colorectal cancer. Moreover, the expression levels of the 4 hub genes were consistent with the TCGA data sets. Briefly, the new hub genes identified in the present research will contribute to improving our understanding as to the molecular mechanisms of CRC carcinogenesis and progression, thus improving the chance to identify the suitable targets for detecting and treating CRC promptly.