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Identification of disrupted pathways associated with colon cancer based on combining protein-protein interactions and
1Department of Operating Room, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
Objective:
The objective of this paper was to identify the disrupted pathways associated with colon cancer at a network level based on protein-protein interaction (PPI) network and pathway analysis.
Materials And Methods:
First of all, the Affymetrix microarray data of colon cancer, human PPIs relationships, and human pathways existed in the database were recruited and preprocessed. Second, differentially expressed genes (DEGs) between colon cancer and normal controls were identified. In the following, an objective PPI network was constructed using these DEGs. Ultimately, we calculated the disrupted pathways based on the intersection between pathway network and the objective network. Meanwhile, the topological centrality (degree) analysis was performed to explore the hub genes in the objective network.
Results:
In our study, an objective network consisted of 2288 PPI pairs by 574 DEGs were constructed. In addition, ten disrupted pathways whose number of intersection was not <22 between objective network and each pathway, as well as P < 0.05, was selected. Furthermore, a total of 22 hub genes in the objective network were selected based on degree >30. Last, seven out of the above ten pathways were validated to involve in the intersections of pathway network and objective network. Moreover, cell cycle was the most significant disrupted pathway.
Conclusions:
We successfully identified several biologically disrupted pathways, and these pathways might be potential biomarkers in detection and treatment for colon cancer.
Insights
This study identified disrupted biological pathways in colon cancer using protein-protein interaction networks. These pathways, including the cell cycle, may serve as potential biomarkers for colon cancer detection and treatment.
Area of Science:
- Genomics and Bioinformatics
- Cancer Biology
- Systems Biology
Background:
- Colon cancer is a significant global health concern.
- Understanding molecular mechanisms is crucial for effective diagnosis and treatment.
- Network-level analysis offers insights into complex diseases like colon cancer.
Purpose of the Study:
- To identify disrupted pathways in colon cancer using protein-protein interaction (PPI) network and pathway analysis.
- To pinpoint key genes (hub genes) within these disrupted pathways.
- To explore the potential of identified pathways as biomarkers for colon cancer.
Main Methods:
- Utilized Affymetrix microarray data for colon cancer and integrated human PPI and pathway databases.
- Identified differentially expressed genes (DEGs) between colon cancer and normal samples.
- Constructed a PPI network from DEGs and analyzed pathway intersections to find disrupted pathways and hub genes.
Main Results:
- A PPI network with 2288 interactions and 574 DEGs was constructed.
- Ten disrupted pathways with statistical significance (P < 0.05) were selected.
- Twenty-two hub genes were identified, and the cell cycle pathway was highlighted as the most significant disrupted pathway.
Conclusions:
- Successfully identified several biologically disrupted pathways in colon cancer.
- These pathways show potential as biomarkers for colon cancer detection and therapeutic strategies.
- Network-based analysis provides a valuable approach for understanding colon cancer pathogenesis.
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