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

• Published in: PloS one 2012-10, Vol.7 (10), p.e46908-e46908
• Main Authors: Honda, Kazufumi, Okusaka, Takuji, Felix, Klaus, Nakamori, Shoji, Sata, Naohiro, Nagai, Hideo, Ioka, Tatsuya, Tsuchida, Akihiko, Shimahara, Takeshi, Shimahara, Masashi, Yasunami, Yohichi, Kuwabara, Hideya, Sakuma, Tomohiro, Otsuka, Yoshihiko, Ota, Norihito, Shitashige, Miki, Kosuge, Tomoo, Büchler, Markus W, Yamada, Tesshi
• Format: Article
• Language: English
• Subjects: Adult; Amino Acid Sequence; Antibody Specificity; Apolipoprotein AII; Apolipoprotein C-III; Apolipoproteins; Apolipoproteins - blood; Apolipoproteins - chemistry; Apolipoproteins - immunology; Biology; Biomarkers; Blood proteins; Cancer; Cancer patients; Cancer therapies; Care and treatment; Chemotherapy; Disease; Female; Gene expression; Hospitals; Humans; Institutions; Invasiveness; Ionization; Lipids; Male; Mass spectrometry; Mass spectroscopy; Medical diagnosis; Medical prognosis; Medical screening; Medicine; Middle Aged; Molecular Sequence Data; Pancreas; Pancreatic cancer; Pancreatic carcinoma; Pancreatic Neoplasms - blood; Patients; Prognosis; Protein Multimerization; Protein Structure, Quaternary; Proteins; Proteomics; Quadrupoles; Reproducibility of Results; Scientific imaging; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Surgery; Tandem Mass Spectrometry; Tomography
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0046908

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. 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. 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. 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.