An automated micro-total immunoassay system for measuring cancer-associated α2,3-linked sialyl N-glycan-carrying prostate-specific antigen may improve the accuracy of prostate cancer diagnosis

Tomokazu Ishikawa, Tohru Yoneyama, Yuki Tobisawa, Shingo Hatakeyama, Tatsuo Kurosawa, Kenji Nakamura, Shintaro Narita, Koji Mitsuzuka, Wilhelmina Duivenvoorden, Jehonathan H. Pinthus, Yasuhiro Hashimoto, Takuya Koie, Tomonori Habuchi, Yoichi Arai, Chikara Ohyama

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15 Citations (Scopus)

Abstract

The low specificity of the prostate-specific antigen (PSA) for early detection of prostate cancer (PCa) is a major issue worldwide. The aim of this study to examine whether the serum PCa-associated α2,3-linked sialyl N-glycan-carrying PSA (S2,3PSA) ratio measured by automated micro-total immunoassay systems (µTAS system) can be applied as a diagnostic marker of PCa. The µTAS system can utilize affinity-based separation involving noncovalent interaction between the immunocomplex of S2,3PSA and Maackia amurensis lectin to simultaneously determine concentrations of free PSA and S2,3PSA. To validate quantitative performance, both recombinant S2,3PSA and benign-associated α2,6-linked sialyl N-glycan-carrying PSA (S2,6PSA) purified from culture supernatant of PSA cDNA transiently-transfected Chinese hamster ovary (CHO)-K1 cells were used as standard protein. Between 2007 and 2016, fifty patients with biopsy-proven PCa were pair-matched for age and PSA levels, with the same number of benign prostatic hyperplasia (BPH) patients used to validate the diagnostic performance of serum S2,3PSA ratio. A recombinant S2,3PSA-and S2,6PSA-spiked sample was clearly discriminated by µTAS system. Limit of detection of S2,3PSA was 0.05 ng/mL and coefficient variation was less than 3.1%. The area under the curve (AUC) for detection of PCa for the S2,3PSA ratio (%S2,3PSA) with cutoff value 43.85% (AUC; 0.8340) was much superior to total PSA (AUC; 0.5062) using validation sample set. Although the present results are preliminary, the newly developed µTAS platform for measuring %S2,3PSA can achieve the required assay performance specifications for use in the practical and clinical setting and may improve the accuracy of PCa diagnosis. Additional validation studies are warranted.

Original languageEnglish
Article number470
JournalInternational journal of molecular sciences
Volume18
Issue number2
DOIs
Publication statusPublished - 2017 Feb 22

Keywords

  • Biomaker
  • Maackia amurensis lectin (MAA) lectin
  • Prostate-specific antigen
  • α2,3-linked sialyl N-glycan

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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    Ishikawa, T., Yoneyama, T., Tobisawa, Y., Hatakeyama, S., Kurosawa, T., Nakamura, K., Narita, S., Mitsuzuka, K., Duivenvoorden, W., Pinthus, J. H., Hashimoto, Y., Koie, T., Habuchi, T., Arai, Y., & Ohyama, C. (2017). An automated micro-total immunoassay system for measuring cancer-associated α2,3-linked sialyl N-glycan-carrying prostate-specific antigen may improve the accuracy of prostate cancer diagnosis. International journal of molecular sciences, 18(2), [470]. https://doi.org/10.3390/ijms18020470