Abstract
BackgroundAmong the more common human malignancies, invasive ductal carcinoma of the pancreas has the worst prognosis. The poor outcome seems to be attributable to difficulty in early detection.MethodsWe compared the plasma protein profiles of 112 pancreatic cancer patients with those of 103 sex- and age-matched healthy controls (Cohort 1) using a newly developed matrix-assisted laser desorption/ionization (oMALDI) QqTOF (quadrupole time-of-flight) mass spectrometry (MS) system.ResultsWe found that hemi-truncated apolipoprotein AII dimer (ApoAII-2; 17252 m/z), unglycosylated apolipoprotein CIII (ApoCIII-0; 8766 m/z), and their summed value were significantly decreased in the pancreatic cancer patients [P = 1.36×10−21, P = 4.35×10−14, and P = 1.83×10−24 (Mann-Whitney U-test); area-under-curve values of 0.877, 0.798, and 0.903, respectively]. The significance was further validated in a total of 1099 plasma/serum samples, consisting of 2 retrospective cohorts [Cohort 2 (n = 103) and Cohort 3 (n = 163)] and a prospective cohort [Cohort 4 (n = 833)] collected from 8 medical institutions in Japan and Germany.ConclusionsWe have constructed a robust quantitative MS profiling system and used it to validate alterations of modified apolipoproteins in multiple cohorts of patients with pancreatic cancer.
Highlights
With a 5-year survival rate of less than 10%, invasive ductal carcinoma of the pancreas has the worst prognosis among the more common human malignancies [1,2,3]
We previously found a plasma biomarker set that was able to distinguish pancreatic cancer patients including those with stage I and II disease from healthy individuals by mass spectrometry (MS)-based proteomics [5]
Patient Samples Four cohorts consisting of a total of 1314 plasma or serum samples were collected at the following medical institutions in two countries (Japan and Germany) (Tables S1 and S2): Cohort 1. 215 plasma samples [sex- and age-matched patients with histologically or cytologically proven pancreatic ductal adenocarcinoma (n = 103) and healthy controls (n = 112)] collected at the National Cancer Center Hospital (NCCH) (Tokyo, Japan) and Tokyo Medical University Hospital (TMUH) (Tokyo, Japan) between August 2002 and February 2005, as reported previously [5]
Summary
With a 5-year survival rate of less than 10%, invasive ductal carcinoma of the pancreas has the worst prognosis among the more common human malignancies [1,2,3]. The poor outcome of pancreatic cancer patients seems to be attributable to difficulty in early detection. Enhanced computed tomography (CT) and positron emission tomography (PET) are useful for the diagnosis of pancreatic diseases, but these modalities are potentially hazardous and would probably be too laborintensive and cost-ineffective for mass screening, because of the relatively low incidence of pancreatic cancer. Among the more common human malignancies, invasive ductal carcinoma of the pancreas has the worst prognosis. The poor outcome seems to be attributable to difficulty in early detection
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