title: Increased circulating cell signalling phosphoproteins in sera are useful for the detection of pancreatic cancer.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of General Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. stakano@faculty.chiba-u.jp
authors.forename: S
authors.initials: S
authors.lastname: Takano
authors.forename: K
authors.initials: K
authors.lastname: Sogawa
authors.forename: H
authors.initials: H
authors.lastname: Yoshitomi
authors.forename: T
authors.initials: T
authors.lastname: Shida
authors.forename: K
authors.initials: K
authors.lastname: Mogushi
authors.forename: F
authors.initials: F
authors.lastname: Kimura
authors.forename: H
authors.initials: H
authors.lastname: Shimizu
authors.forename: H
authors.initials: H
authors.lastname: Yoshidome
authors.forename: M
authors.initials: M
authors.lastname: Ohtsuka
authors.forename: A
authors.initials: A
authors.lastname: Kato
authors.forename: T
authors.initials: T
authors.lastname: Ishihara
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: O
authors.initials: O
authors.lastname: Yokosuka
authors.forename: F
authors.initials: F
authors.lastname: Nomura
authors.forename: M
authors.initials: M
authors.lastname: Miyazaki
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D016000:Cluster Analysis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D008297:Male; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis*; D010195:Pancreatitis / Q000097:blood; D010750:Phosphoproteins / Q000097:blood*; D010766:Phosphorylation; D040901:Proteomics / Q000379:methods; D015398:Signal Transduction
chemical_list: D014408:Biomarkers, Tumor; D010750:Phosphoproteins; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases