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. 2015 Oct;36(4):923-30.
doi: 10.3892/ijmm.2015.2298. Epub 2015 Jul 30.

In-depth analysis of the critical genes and pathways in colorectal cancer

Fuguo Liu  1 , Fengzhi Ji  1 , Yuling Ji  2 , Yueping Jiang  1 , Xueguo Sun  1 , Yanyan Lu  1 , Lingyun Zhang  1 , Yue Han  1 , Xishuang Liu  1
Affiliations

In-depth analysis of the critical genes and pathways in colorectal cancer

Fuguo Liu et al. Int J Mol Med. 2015 Oct.

Abstract

The present study aimed to investigate the molecular targets for colorectal cancer (CRC). Differentially expressed genes (DEGs) were screened between CRC and matched adjacent noncancerous samples. GENETIC_ASSOIATION_DB_DISEASE analysis was performed to identify CRC genes from the identified DEGs using the Database for Annotation, Visualization and Integrated Discovery, followed by Gene Οntology (GO) and Kyoto Encyclopedia of Genes and Genomes analysis for the CRC genes. A protein‑protein interaction (PPI) network was constructed for the CRC genes, followed by determination and analysis of the hub genes, in terms of the protein domains and spatial structure. In total, 35 CRC genes were determined, including 19 upregulated and 16 downregulated genes. Downregulated N‑acetyltransferase (NAT)1 and NAT2 were enriched in the caffeine metabolism pathway. The downregulated and upregulated genes were enriched in a number of GO terms and pathways, respectively. Cyclin D1 (CCND1) and proliferating cell nuclear antigen (PCNA) were identified as the hub genes in the PPI network. The C‑terminal and N‑terminal domains were similar in PCNA, but different in CCND1. The results suggested PCNA, CCND1, NAT1 and NAT2 for use as biomarkers to enable early diagnosis and monitoring of CRC. These results form a basis for developing therapies, which target the unique protein domains of PCNA and CCND1.

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Figures

Figure 1
Figure 1
Box plot for the gene expression data prior to normalization. Expression values were determined using Affy package in R software. The black bar indicates the median value.
Figure 2
Figure 2
Box plot for the gene expression data following normalization. Expression values were determined using Affy package in R software, followed by normalization using the robust multiarray average algorithm The black bar indicates the median value.
Figure 3
Figure 3
Identification of critical genes. (A) Analysis of the DEGs identified between the CRC and normal samples. Horizontal axis, alterations of gene expression; vertical axis, number of genes. (B) Analysis of the 35 identified CRC genes. Horizontal axis, alterations of gene expression; vertical axis, number of genes. DEGs, differentially expressed genes. MF, molecular function; BP, biological process; CC. cellular component.
Figure 4
Figure 4
GO enrichment analysis of the upregulated colorectal cancer genes. Diamond, categories of GO terms; square, GO terms. GO, Gene Οntology; BP, biological process; CC, cellular component. A blue line links a diamond (GO term) and a square (GO category). It means that the diamond (GO term) belongs a square (GO category).
Figure 5
Figure 5
GO enrichment analysis of the downregulated colorectal cancer genes. Diamond, categories of GO terms; square, GO terms. GO, Gene Οntology. A blue line links a diamond (GO term) and a square (GO category). It means that the diamond (GO term) belongs a square (GO category).
Figure 6
Figure 6
PPI network constructed using the colorectal cancer genes. Red round nodes, upregulated genes; green round nodes, downregulated genes; diamond nodes, hub genes. PPI, protein-protein interaction. A blue line indicates the interaction between two proteins that are linked by the blue line.
Figure 7
Figure 7
Spatial structure of the C-terminal of proliferating cell nuclear antigen. The prominent colored frame represents the spatial structure of the protein domain corresponding to the coding region of the gene.
Figure 8
Figure 8
Spatial structure of the N-terminal of proliferating cell nuclear antigen. The prominent colored frame represents the spatial structure of the protein domain corresponding to the coding region of the gene.
Figure 9
Figure 9
Spatial structure of the C-terminal of cyclin D1. The prominent colored frame stands for the spatial structure of the protein domain corresponding to the coding region of the gene.
Figure 10
Figure 10
Spatial structure of the N-terminal of cyclin D1. The prominent colored frame represents the spatial structure of the protein domain corresponding to the coding region of the gene.
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