Identification of key pathways and genes in colorectal cancer using bioinformatics analysis

Abstract

Colorectal cancer (CRC) is the most common malignant tumor of digestive system. The aim of this study was to identify gene signatures during CRC and uncover their potential mechanisms. The gene expression profiles of GSE21815 were downloaded from GEO database. The GSE21815 dataset contained 141 samples, including 132 CRC and 9 normal colon epitheliums. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software. In total, 3500 DEGs were identified in CRC, including 1370 up-regulated genes and 2130 down-regulated genes. GO analysis results showed that up-regulated DEGs were significantly enriched in biological processes (BP), including cell cycle, cell division, and cell proliferation; the down-regulated DEGs were significantly enriched in biological processes, including immune response, intracellular signaling cascade and defense response. KEGG pathway analysis showed the up-regulated DEGs were enriched in cell cycle and DNA replication, while the down-regulated DEGs were enriched in drug metabolism, metabolism of xenobiotics by cytochrome P450, and retinol metabolism pathways. The top 10 hub genes, GNG2, AGT, SAA1, ADCY5, LPAR1, NMU, IL8, CXCL12, GNAI1, and CCR2 were identified from the PPI network, and sub-networks revealed these genes were involved in significant pathways, including G protein-coupled receptors signaling pathway, gastrin-CREB signaling pathway via PKC and MAPK, and extracellular matrix organization. In conclusion, the present study indicated that the identified DEGs and hub genes promote our understanding of the molecular mechanisms underlying the development of CRC, and might be used as molecular targets and diagnostic biomarkers for the treatment of CRC.

Expression profiling of colorectal cancer cells reveals inhibition of DNA replication licensing by extracellular calcium

“…It seems that the calcium-dependence of colorectal tumor cells changes. On one hand, those Ca 2+ -dependent processes that inhibit proliferation are suppressed in colorectal tumors [53]. On the other hand, Ca 2+ -dependent processes that correlate with increased cell proliferation, invasion, and survival of tumor cells, such as store-operated Ca 2+ entry and store-operated currents are largely enhanced in tumor cells, while the level of Ca 2+ in internal stores is low [54].…”

Identification of key pathways and biomarkers in sorafenib‑resistant hepatocellular carcinoma using bioinformatics analysis

“…DAVID contains a series of functional annotation programs to explore abundant biological messages of genes and information mapped in DAVID was important for the completion of high-throughput gene functional analysis (11). P<0.05 was considered to indicate a statistically significant difference (12). …”

“…The PPI network was built using Cytoscape (). In addition, higher-degree nodes were regarded as hub nodes (12). Sub-modules of the PPI network were analyzed by Molecular Complex Detection (MCODE; Version 1.4.2; by Bader Lab, department of Biochemistry, University of Toronto; Toronto, Canada) (13), with the criteria set as follows: number of nodes >4 and MCODE score >3.…”

MicroRNA-125b-1-3p mediates intervertebral disc degeneration in rats by targeting teashirt zinc finger homeobox 3

“…The GSE63492 dataset contained 10 samples in total, 5 of which were samples from patients with IDD and the other 5 were tissues from individuals with normal discs. A total of 134 micro (mi)RNAs (DEMs) have been identified as differentially expressed in intervertebral disc degeneration (IDD) by gene expression profiling studies using microarray technology (22). MicroRNA (miR)3150A was selected from the upregulated miRNAs and miR-125b-1-3p was selected from the downregulated miRNAs as these were identified as the most significant.…”