Screening key genes and signaling pathways in colorectal cancer by integrated bioinformatics analysis

Abstract

The aim of the present study was to identify potential key genes associated with the progression and prognosis of colorectal cancer (CRC). Differentially expressed genes (DEGs) between CRC and normal samples were screened by integrated analysis of gene expression profile datasets, including the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted to identify the biological role of DEGs. In addition, a protein-protein interaction network and survival analysis were used to identify the key genes. The profiles of GSE9348, GSE22598 and GSE113513 were downloaded from the GEO database. A total of 405 common DEGs were identified, including 236 down- and 169 upregulated. GO analysis revealed that the downregulated DEGs were mainly enriched in ‘detoxification of copper ion’ [biological process, (BP)], ‘oxidoreductase activity, acting on CH-OH group of donors, NAD or NADP as acceptor’ [molecular function, (MF)] and ‘brush border’ [cellular component, (CC)]. Upregulated DEGs were mainly involved in ‘nuclear division’ (BP), ‘snoRNA binding’ (MF) and ‘nucleolar part’ (CC). KEGG pathway analysis revealed that DEGs were mainly involved in ‘mineral absorption’, ‘nitrogen metabolism’, ‘cell cycle’ and ‘caffeine metabolism’. A PPI network was constructed with 268 nodes and 1,027 edges. The top one module was selected, and it was revealed that module-related genes were mainly enriched in the GO terms ‘sister chromatid segregation’ (BP), ‘chemokine activity’ (MF), and ‘condensed chromosome (CC)’. The KEGG pathway was mainly enriched in ‘cell cycle’, ‘progesterone-mediated oocyte maturation’, ‘chemokine signaling pathway’, ‘IL-17 signaling pathway’, ‘legionellosis’, and ‘rheumatoid arthritis’. DNA topoisomerase II-α (TOP2A), mitotic arrest deficient 2 like 1 (MAD2L1), cyclin B1 (CCNB1), checkpoint kinase 1 (CHEK1), cell division cycle 6 (CDC6) and ubiquitin conjugating enzyme E2 C (UBE2C) were indicated as hub genes. Furthermore, survival analysis revealed that TOP2A, MAD2L1, CDC6 and CHEK1 may serve as prognostic biomarkers in CRC. The present study provided insights into the molecular mechanism of CRC that may be useful in further investigations.

Gene Expression Alterations and Molecular Analysis of CHEK1 in Solid Tumors

“…In light of this, novel cancer-related genes may still be identified in the amplified regions. Previous studies have shown that CHEK1 is involved in various tumors by influencing the target genes or signal pathway, which is consistent with this study [12,[63][64][65][66].…”

Genomic analyses identify significant molecules and biological processes in colorectal cancer cells with DNA damage

“…Xiang Ding et al found PLK1 is a critical gene in colorectal cancer, which is positively correlated with the development of cancer 49 . Chang Yu et al found CDC6 may serve as a prognostic biomarker in colorectal cancer 50 .…”

Role of Stress-Survival Pathways and Transcriptomic Alterations in Progression of Colorectal Cancer: A Health Disparities Perspective

“…The ribonucleotide reductase regulatory subunit m2 ( RRM2 ) gene, which is a part of the cell cycle and p53 signaling pathway, is also known to be overexpressed in CRC [ 18 ], and has been correlated with the poorly differentiated type, invasion depth, and tumor node metastasis stages in CRC [ 18 ]. Among the other cell cycle and p53 signaling pathway genes are DNA topoisomerase 2-alpha ( TOP2A ) [ 58 ], cell division cycle 6 ( CDC6 ) [ 59 , 60 ], nucleolar and spindle associated protein 1 ( NUSAP1 ) [ 61 ], centrosomal protein 55 ( CEP55 ) [ 62 ], budding uninhibited by benzimidazoles 1 ( BUB1 ) [ 63 ], and the mitotic arrest deficient 2 like 1 ( MAD2L1 ) [ 63 ], which are known to be differentially expressed in CRC, and are related to the aggressive tumor phenotypes and advanced tumor stages.…”