Increased circulating cell signalling phosphoproteins in sera are useful for the detection of pancreatic cancer.
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.
Takano
S
S
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
Sogawa
K
K
Yoshitomi
H
H
Shida
T
T
Mogushi
K
K
Kimura
F
F
Shimizu
H
H
Yoshidome
H
H
Ohtsuka
M
M
Kato
A
A
Ishihara
T
T
Tanaka
H
H
Yokosuka
O
O
Nomura
F
F
Miyazaki
M
M
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
D014408:Biomarkers, Tumor; D010750:Phosphoproteins; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases