Altered plasma apolipoprotein modifications in patients with pancreatic cancer: protein characterization and multi-institutional validation

PLoS One. 2012;7(10):e46908. doi: 10.1371/journal.pone.0046908. Epub 2012 Oct 8.

Abstract

Background: 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.

Methods: We 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.

Results: We 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.

Conclusions: We 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Antibody Specificity
  • Apolipoproteins / blood*
  • Apolipoproteins / chemistry
  • Apolipoproteins / immunology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Pancreatic Neoplasms / blood*
  • Protein Multimerization
  • Protein Structure, Quaternary
  • Reproducibility of Results
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Tandem Mass Spectrometry

Substances

  • Apolipoproteins

Grant support

This work was supported by the Program for Promotion of Fundamental Studies in Health Sciences conducted by the National Institute of Biomedical Innovation of Japan, Health and Labour Sciences Research Grants from the Ministry of Health, Labor and Welfare of Japan, the National Cancer Center Research and Development Fund, and in part by the German Research Foundation (DFG) (FE 940/2-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.