Increased circulating cell signaling phosphoproteins in sera are useful for early detection and the tailor-made therapy for pancreatic and biliary duct cancer patients.

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Intracellular phosphoprotein activation significantly regulatescancer progression. We investigated the serum phosphoprotein profile involved in pancreatic cancer by a novel approach that comprehensively measured serum phosphoproteins levels, and clinically applied this method to the detection of pancreatic cancer. We analyzed the serum phosphoproteins that comprised cancer cellular signal pathways by comparing sera from pancreatic cancer patients and benign controls including healthy volunteers and pancreatitis patients. Hierarchical clustering analysis between pancreatic cancer patients and healthy volunteers revealed differential pathway-specific profiles. In particular, the components of the extracellular signal-regulated kinase (ERK) signaling pathway were significantly increased in the sera from pancreatic cancer patients compared with healthy volunteers. The positive rate of p-ERKI/2 (82%) was found to be superior to that of CA19-9 (53%) for early stage pancreatic cancer. For the combination of these serum levels, the area under the receiver-operator-characteristics curves were showing significant ability to distinguish between the two populations in independent validation set, and between cancer and non-cancer populations in another validation set. The comprehensive measurement of serum cell signal phosphoproteins is useful for, the detection of pancreatic cancer. Further investigations will lead to the implementation of tailor-made molecular-targeted therapeutics.