Identification of crucial genes and pathways associated with colorectal cancer by bioinformatics analysis

Abstract

Colorectal cancer (CRC) is a prevalent malignant tumour type arising from the colon and rectum. The present study aimed to explore the molecular mechanisms of the development and progression of CRC. Initially, differentially expressed genes (DEGs) between CRC tissues and corresponding non-cancerous tissues were obtained by analysing the GSE15781 microarray dataset. The Database for Annotation, Visualization and Integrated Discovery was then utilized for functional and pathway enrichment analysis of the DEGs. Subsequently, a protein-protein interaction (PPI) network was created using the Search Tool for the Retrieval of Interacting Genes and Proteins database and visualized by Cytoscape software. Furthermore, CytoNCA, a Cytoscape plugin, was used for centrality analysis of the PPI network to identify crucial genes. Finally, UALCAN was employed to validate the expression of the crucial genes and to estimate their effect on the survival of patients with colon cancer by Kaplan-Meier curves and log-rank tests. A total of 1,085 DEGs, including 496 upregulated and 589 downregulated genes, were screened out. The DEGs identified were enriched in various pathways, including 'metabolic pathway', 'cell cycle', 'DNA replication', 'nitrogen metabolism', 'p53 signalling' and 'fatty acid degradation'. PPI network analysis suggested that interleukin-6, MYC, NOTCH1, inhibin subunit βA (INHBA), CDK1, cyclin (CCN)B1 and CCNA2 were crucial genes, and their expression levels were markedly upregulated. Survival analysis suggested that upregulated INHBA significantly decreased the survival probability of patients with CRC. Conversely, upregulation of CCNB1 and CCNA2 expression levels were associated with increased survival probabalities. The identified DEGs, particularly the crucial genes, may enhance the current understanding of the genesis and progression of CRC, and certain genes, including INHBA, CCNB1 and CCNA2, may be candidate diagnostic and prognostic markers, as well as targets for the treatment of CRC.

Inflammatory Serum Biomarkers in Colorectal Cancer in Kazakhstan Population

“…Excessive expression of IL-6 is the most common finding when investigating the association of inflammation and cancer. IL-6 regulates numerous signaling pathways, including apoptosis, survival, proliferation, angiogenesis, invasion, and metastasis [ 11 – 13 ]. In a number of studies, IL-6 acts as a protector of cancer cells from therapy-induced DNA damage, oxidative stress, and apoptosis, contributing to repair [ 11 ].…”

Identification prognosis-associated immune genes in colon adenocarcinoma

“…FABP4 plays a crucial role in regulating lipid metabolism and adipocyte differentiation associated with the tumor suppressor, PTEN [ 34 ]. FABP4 and ADIPOQ have been reported to increase the risk of colorectal neoplasia related to the COAD survival probability [ 35 , 36 ]. Dudgeon et al found that UCN can inhibit COAD cell growth via inducing apoptosis by PUMA and a p53 target [ 37 ].…”

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.…”

“…Apart from the genes associated with stress survival pathways, genes encoding for different kinases have also been seen to be differentially expressed in various CRC cases. The top candidates include serine/threonine-protein kinase ( PLK1 ) [ 19 , 103 ], aurora kinase A ( AURKA ) [ 63 ], checkpoint kinase 1 ( CHEK1 ) [ 78 ], and maternal embryonic leucine zipper kinase ( MELK ) [ 100 ]. These genes are seen to control the proliferation, migration, invasion of CRC cells, prognosis, or metastasis of CRC.…”