Identification of genes involved in the four stages of colorectal cancer: Gene expression profiling

Mol Cell Probes. 2018 Feb:37:39-47. doi: 10.1016/j.mcp.2017.11.004. Epub 2017 Nov 24.

Abstract

Background: Colorectal cancer (CRC) is a common cancer with high morbidity and mortality. However, its molecular mechanism is not clear, nor the genes related to CRC stages.

Methods: Gene expression data in CRC and healthy colorectal tissues were obtained from gene expression omnibus. Limma package was used to identify the differentially expressed genes (DEGs) between control and CRC (stage I, II, III, and IV), obtaining 4 DEG sets. VennPlex was utilized to find all DEGs and intersection DEGs. Functional interactions between all DEGs and protein-protein interactions (PPIs) between intersection DEGs were analyzed using ReactomeFIViz and STRING, respectively, and networks were visualized. Known CRC-related genes were down-loaded from Comparative Toxicogenomics Database and mapped to PPI network.

Results: Totally, 851, 760, 729, and 878 DEGs were found between control and CRC stage I, II, III, and IV, respectively. Taken together, 1235 DEGs were found, as well as 128 up-regulated intersection DEGs, 365 down-regulated intersection DEGs, and 0 contra-regulated DEG. A functional interaction network of all DEGs and a PPI network of intersection DEGs were constructed, in which CDC20, PTTG1, and MAD2L1 interacted with BUB1B; UGT2B17 interacted with ADH1B; MCM7 interacted with MCM2. BUB1B, ADH1B, and MCM2 were known CRC-related genes. Gradually upregulated expressions of CDC20, PTTG1, MAD2L1, UGT2B17, and MCM7 in stage I, II, III, and IV CRC were confirmed by using quantitative PCR. Besides, up-regulated intersection DEGs enriched in pathways about Cell cycle, DNA replication, and p53 signaling.

Conclusion: CDC20, PTTG1, MAD2L1, UGT2B17, and MCM7 might be CRC stage-related genes.

Keywords: Cancer stage; Colorectal cancer; Functional interaction; Pathway enrichment analysis; Protein-protein interaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / analysis
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Cdc20 Proteins / analysis
  • Cdc20 Proteins / genetics
  • Cdc20 Proteins / metabolism
  • Cell Cycle Proteins / analysis
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology*
  • Databases, Genetic
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic
  • Glucuronosyltransferase / analysis
  • Glucuronosyltransferase / genetics
  • Glucuronosyltransferase / metabolism
  • Humans
  • Minichromosome Maintenance Complex Component 7 / analysis
  • Minichromosome Maintenance Complex Component 7 / genetics
  • Minichromosome Maintenance Complex Component 7 / metabolism
  • Minor Histocompatibility Antigens / analysis
  • Minor Histocompatibility Antigens / genetics
  • Minor Histocompatibility Antigens / metabolism
  • Neoplasm Staging
  • Nuclear Proteins / analysis
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Protein Interaction Maps
  • Securin / analysis
  • Securin / genetics
  • Securin / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Cdc20 Proteins
  • Cell Cycle Proteins
  • MAD2L1BP protein, human
  • Minor Histocompatibility Antigens
  • Nuclear Proteins
  • Securin
  • pituitary tumor-transforming protein 1, human
  • CDC20 protein, human
  • Glucuronosyltransferase
  • UGT2B17 protein, human
  • MCM7 protein, human
  • Minichromosome Maintenance Complex Component 7