Increased circulating cell signalling phosphoproteins in sera are useful for the detection of pancreatic cancer

Br J Cancer. 2010 Jul 13;103(2):223-31. doi: 10.1038/sj.bjc.6605734. Epub 2010 Jun 15.

Abstract

Background: Intracellular phosphoprotein activation significantly regulates cancer progression. However, the significance of circulating phosphoproteins in the blood remains unknown. We investigated the serum phosphoprotein profile involved in pancreatic cancer (PaCa) by a novel approach that comprehensively measured serum phosphoproteins levels, and clinically applied this method to the detection of PaCa.

Methods: We analysed the serum phosphoproteins that comprised cancer cellular signal pathways by comparing sera from PaCa patients and benign controls including healthy volunteers (HVs) and pancreatitis patients.

Results: Hierarchical clustering analysis between PaCa patients and HVs revealed differential pathway-specific profiles. In particular, the components of the extracellular signal-regulated kinase (ERK) signalling pathway were significantly increased in the sera of PaCa patients compared with HVs. The positive rate of p-ERK1/2 (82%) was found to be superior to that of CA19-9 (53%) for early stage PaCa. For the combination of these serum levels, the area under the receiver-operator characteristics curves was showing significant ability to distinguish between the two populations in independent validation set, and between cancer and non-cancer populations in another validation set.

Conclusion: The comprehensive measurement of serum cell signal phosphoproteins is useful for the detection of PaCa. Further investigations will lead to the implementation of tailor-made molecular-targeted therapeutics.

Publication types

  • Comparative Study
  • Evaluation Study

MeSH terms

  • Biomarkers, Tumor / blood*
  • Cluster Analysis
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Humans
  • MAP Kinase Kinase Kinases / metabolism
  • Male
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatitis / blood
  • Phosphoproteins / blood*
  • Phosphorylation
  • Proteomics / methods
  • Signal Transduction*

Substances

  • Biomarkers, Tumor
  • Phosphoproteins
  • Extracellular Signal-Regulated MAP Kinases
  • MAP Kinase Kinase Kinases