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Protein-protein interaction analysis of distinct molecular pathways in two subtypes of colorectal carcinoma.

Chen H, Fang Y, Zhu H, Li S, Wang T, Gu P, Fang X, Wu Y, Liang J, Zeng Y, Zhang L, Qiu W, Zhang L, Yi X - Mol Med Rep (2014)

Bottom Line: The interaction between pathways was also analyzed in CCRC based on the PPI network.The PPI network showed that tumour necrosis factor receptor-associated factor 6 (TRAF6) and atrophin 1 (ATN1) were the most central genes in the network, with respective degrees of node predicted at 90 and 88.Furthermore, TRAF6 and ATN1 may be promising biomarkers for the distinction between serrated and conventional CRC.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Central Hospital of Shanghai Zhabei District, Shanghai 200070, P.R. China.

ABSTRACT
The aim of this study was to identify the molecular events that distinguish serrated colorectal carcinoma (SCRC) from conventional colorectal carcinoma (CCRC) through differential gene expression, pathway and protein-protein interaction (PPI) network analysis. The GSE4045 and GSE8671 microarray datasets were downloaded from the Gene Expression Omnibus database. We identified the genes that are differentially expressed between SCRC and normal colon tissues, CCRC and healthy tissues, and between SCRC and CCRC using Student's t-tests and Benjamini‑Hochberg (BH) multiple testing corrections. The differentially expressed genes (DEGs) were then mapped to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and their enrichment for specific pathways was investigated using the Database for Annotation, Visualization and Integrated Discovery (DAVID) tool with a significance threshold of 0.1. Analysis of the potential interactions between the protein products of 220 DEGs (between CCRC and SCRC) was performed by constructing a PPI network using data from the high performance RDF database (P<0.1). The interaction between pathways was also analyzed in CCRC based on the PPI network. Our study identified thousands of genes differentially expressed in SCRC and CCRC compared to healthy tissues. The DEGs in SCRC and CCRC were enriched in cell cycle, DNA replication, and base excision repair pathways. The proteasome pathway was significantly enriched in SCRC but not in CCRC after BH adjustment. The PPI network showed that tumour necrosis factor receptor-associated factor 6 (TRAF6) and atrophin 1 (ATN1) were the most central genes in the network, with respective degrees of node predicted at 90 and 88. In conclusion, the preoteasome pathway was shown to be specifically enriched in SCRC. Furthermore, TRAF6 and ATN1 may be promising biomarkers for the distinction between serrated and conventional CRC.

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Pathway network in conventional colorectal carcinoma. Nodes represent significantly enriched pathways. Edges represent the interaction between pathways.
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f3-mmr-10-06-2868: Pathway network in conventional colorectal carcinoma. Nodes represent significantly enriched pathways. Edges represent the interaction between pathways.

Mentions: There was no interactions among pathways involved in SCRC (data not shown). However, there was some interaction between significantly enriched pathways involved in CCRC (Fig. 3). In the interaction network, p53 signaling, cell cycle and mismatch repair pathways showed the highest degree of nodes.


Protein-protein interaction analysis of distinct molecular pathways in two subtypes of colorectal carcinoma.

Chen H, Fang Y, Zhu H, Li S, Wang T, Gu P, Fang X, Wu Y, Liang J, Zeng Y, Zhang L, Qiu W, Zhang L, Yi X - Mol Med Rep (2014)

Pathway network in conventional colorectal carcinoma. Nodes represent significantly enriched pathways. Edges represent the interaction between pathways.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4227423&req=5

f3-mmr-10-06-2868: Pathway network in conventional colorectal carcinoma. Nodes represent significantly enriched pathways. Edges represent the interaction between pathways.
Mentions: There was no interactions among pathways involved in SCRC (data not shown). However, there was some interaction between significantly enriched pathways involved in CCRC (Fig. 3). In the interaction network, p53 signaling, cell cycle and mismatch repair pathways showed the highest degree of nodes.

Bottom Line: The interaction between pathways was also analyzed in CCRC based on the PPI network.The PPI network showed that tumour necrosis factor receptor-associated factor 6 (TRAF6) and atrophin 1 (ATN1) were the most central genes in the network, with respective degrees of node predicted at 90 and 88.Furthermore, TRAF6 and ATN1 may be promising biomarkers for the distinction between serrated and conventional CRC.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Central Hospital of Shanghai Zhabei District, Shanghai 200070, P.R. China.

ABSTRACT
The aim of this study was to identify the molecular events that distinguish serrated colorectal carcinoma (SCRC) from conventional colorectal carcinoma (CCRC) through differential gene expression, pathway and protein-protein interaction (PPI) network analysis. The GSE4045 and GSE8671 microarray datasets were downloaded from the Gene Expression Omnibus database. We identified the genes that are differentially expressed between SCRC and normal colon tissues, CCRC and healthy tissues, and between SCRC and CCRC using Student's t-tests and Benjamini‑Hochberg (BH) multiple testing corrections. The differentially expressed genes (DEGs) were then mapped to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and their enrichment for specific pathways was investigated using the Database for Annotation, Visualization and Integrated Discovery (DAVID) tool with a significance threshold of 0.1. Analysis of the potential interactions between the protein products of 220 DEGs (between CCRC and SCRC) was performed by constructing a PPI network using data from the high performance RDF database (P<0.1). The interaction between pathways was also analyzed in CCRC based on the PPI network. Our study identified thousands of genes differentially expressed in SCRC and CCRC compared to healthy tissues. The DEGs in SCRC and CCRC were enriched in cell cycle, DNA replication, and base excision repair pathways. The proteasome pathway was significantly enriched in SCRC but not in CCRC after BH adjustment. The PPI network showed that tumour necrosis factor receptor-associated factor 6 (TRAF6) and atrophin 1 (ATN1) were the most central genes in the network, with respective degrees of node predicted at 90 and 88. In conclusion, the preoteasome pathway was shown to be specifically enriched in SCRC. Furthermore, TRAF6 and ATN1 may be promising biomarkers for the distinction between serrated and conventional CRC.

Show MeSH
Related in: MedlinePlus