Pancreatic cancer is one of the most lethal
tumors, and reliable detection of early-stage
pancreatic cancer and risk diseases for
pancreatic cancer is essential to improve the prognosis. As 260 genes were previously reported to be upregulated in invasive ductal
adenocarcinoma of pancreas (IDACP) cells, quantification of the corresponding
proteins in plasma might be useful for IDACP diagnosis. Therefore, the purpose of the present study was to identify plasma
biomarkers for early detection of IDACP by using two proteomics strategies: antibody-based proteomics and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics. Among the 260 genes, we focused on 130 encoded
proteins with known function for which
antibodies were available. Twenty-three
proteins showed values of the area under the curve (AUC) of more than 0.8 in receiver operating characteristic (ROC) analysis of reverse-phase
protein array (RPPA) data of IDACP patients compared with healthy controls, and these
proteins were selected as
biomarker candidates. We then used our high-throughput selected reaction monitoring or multiple reaction monitoring (SRM/MRM) methodology, together with an automated sample preparation system, micro LC and auto analysis system, to quantify these candidate
proteins in plasma from healthy controls and IDACP patients on a large scale. The results revealed that
insulin-like growth factor-binding protein (
IGFBP)2 and IGFBP3 have the ability to discriminate IDACP patients at an early stage from healthy controls, and IGFBP2 appeared to be increased in risk diseases of pancreatic
malignancy, such as intraductal papillary
mucinous neoplasms (IPMNs). Furthermore, diagnosis of IDACP using the combination of
carbohydrate antigen 19-9 (CA19-9), IGFBP2 and IGFBP3 is significantly more effective than CA19-9 alone. This suggests that IGFBP2 and IGFBP3 may serve as compensatory
biomarkers for CA19-9. Early diagnosis with this marker combination may improve the prognosis of IDACP patients.