Bioinformatic analyses revealed underlying biological functions correlated with oxaliplatin responsiveness

Tumour Biol. 2016 Jan;37(1):583-90. doi: 10.1007/s13277-015-3807-2. Epub 2015 Aug 2.

Abstract

Colorectal cancer is one of the most common cancers worldwide. Surgery is usually the primary treatment for colon cancers that have not spread to distant sites. However, chemotherapy may be considered after surgery to eliminate remaining cancer cells or in case the cancer has a high risk of recurrence. Oxaliplatin is often used in combination regimens such as FOLFOX, CapeOX, and FOLFOXIRI because of the cost-effectiveness of adjuvant treatment for patients and also the good tolerability profile. However, some patients show resistance to oxaliplatin which causes poor treatment outcomes. Most colon cancer studies focused on treatments and patient survival. Some studies focused on genetic associations of specific genes. However, pathway and network analyses of oxaliplatin resistance in colon cancer cells using gene expression patterns are still lacking. We performed a microarray analysis and found that endothelin-1 (EDN1), dishevelled segment polarity protein (DV1), toll-like receptor 5(TLR5), mitogen-activated protein kinase 3 (MAP2K3), phosphatidylinositol-4,5-bisphosphate 3-kinase, and catalytic subunit beta (PIK3CB) were closely related to responsiveness to oxaliplatin treatment. Furthermore, we found that the signal transduction, melanogenesis, and toll-like receptor signaling pathways might be involved in oxaliplatin-resistant colon cancer. These genes and pathways might be potential targets for improving oxaliplatin treatment in colon cancer patients.

Keywords: Bioinformatic analysis; Colon cancer; Network and pathway analysis; Oxaliplatin.

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Cluster Analysis
  • Colonic Neoplasms* / drug therapy
  • Colonic Neoplasms* / genetics
  • Colonic Neoplasms* / metabolism
  • Colonic Neoplasms* / pathology
  • Computational Biology* / methods
  • Databases, Genetic
  • Drug Resistance, Neoplasm
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Regulatory Networks
  • Humans
  • Metabolic Networks and Pathways / drug effects
  • Models, Biological*
  • Organoplatinum Compounds* / pharmacology
  • Organoplatinum Compounds* / therapeutic use
  • Oxaliplatin
  • Protein Interaction Mapping
  • Protein Interaction Maps
  • Signal Transduction / drug effects
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Oxaliplatin