Development of a glycoproteomic strategy to detect more aggressive prostate cancer using lectin-immunoassays for serum fucosylated PSA

Ce Wang, Naseruddin Höti, Tung Shing Mamie Lih, Lori J Sokoll, Rui Zhang, Zhen Zhang, Hui Zhang, Daniel Wan-Yui Chan

Research output: Contribution to journalArticle

Abstract

Background: Prostate-specific antigen (PSA) is commonly used as a serum biomarker for the detection of prostate cancer. However, levels of PSA in serum do not reliably distinguish aggressive prostate cancer from non-aggressive disease. Therefore, there is an urgent need for biomarkers that can differentiate aggressive prostate cancers from non-aggressive phenotypes. Fucosylation is one of the glycosylation-based protein modifications. Previously we demonstrated increased levels of serum fucosylated PSA in patients with aggressive prostate cancer using lectin selection followed by PSA immunoassay. Methods: We developed two lectin-immunoassays, Lens culinaris agglutinin (LCA) and Aleuria aurantia lectin (AAL) followed by clinical PSA immunoassay and investigated the levels of PSA and its fucosylated glycoforms in serum specimens from prostate cancer patients with different Gleason scores. First, we developed standard curves for lectins enrichment, which were applied to lectin-immunoassay for fucosylated PSA-LCA and PSA-AAL quantification in serum samples. Results: Our results showed that both LCA- and AAL-immunoassays detected elevated fucosylated PSA and were correlated with higher Gleason scores but only AAL-immunoassay detected an increased percentage of fucosylated PSA in patient serum with higher Gleason scores. Conclusion: We have developed quantitative lectin-immunoassays for serum fucosylated PSA. Our data demonstrated that fucosylated PSA-AAL, % fucosylated PSA-AAL and fucosylated PSA-LCA levels could be effective biomarkers to differentiate aggressive prostate cancer [especially Gleason 7 (4 + 3) or above] from non-aggressive disease. We believe that application of these lectin-immunoassays to a larger patient population is needed to evaluate the clinical utilities of fucosylated PSA using AAL-PSA and LCA-PSA for aggressive prostate cancer.

Original languageEnglish (US)
Article number13
JournalClinical Proteomics
Volume16
Issue number1
DOIs
StatePublished - Apr 6 2019

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Prostate-Specific Antigen
Immunoassay
Lectins
Prostatic Neoplasms
Serum
Neoplasm Grading
Biomarkers
Glycosylation
Aleuria aurantia lectin

Keywords

  • Fucosylated PSA
  • Glycoproteomic
  • Lectin-immunoassays
  • Prostate cancer

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Development of a glycoproteomic strategy to detect more aggressive prostate cancer using lectin-immunoassays for serum fucosylated PSA. / Wang, Ce; Höti, Naseruddin; Lih, Tung Shing Mamie; Sokoll, Lori J; Zhang, Rui; Zhang, Zhen; Zhang, Hui; Chan, Daniel Wan-Yui.

In: Clinical Proteomics, Vol. 16, No. 1, 13, 06.04.2019.

Research output: Contribution to journalArticle

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abstract = "Background: Prostate-specific antigen (PSA) is commonly used as a serum biomarker for the detection of prostate cancer. However, levels of PSA in serum do not reliably distinguish aggressive prostate cancer from non-aggressive disease. Therefore, there is an urgent need for biomarkers that can differentiate aggressive prostate cancers from non-aggressive phenotypes. Fucosylation is one of the glycosylation-based protein modifications. Previously we demonstrated increased levels of serum fucosylated PSA in patients with aggressive prostate cancer using lectin selection followed by PSA immunoassay. Methods: We developed two lectin-immunoassays, Lens culinaris agglutinin (LCA) and Aleuria aurantia lectin (AAL) followed by clinical PSA immunoassay and investigated the levels of PSA and its fucosylated glycoforms in serum specimens from prostate cancer patients with different Gleason scores. First, we developed standard curves for lectins enrichment, which were applied to lectin-immunoassay for fucosylated PSA-LCA and PSA-AAL quantification in serum samples. Results: Our results showed that both LCA- and AAL-immunoassays detected elevated fucosylated PSA and were correlated with higher Gleason scores but only AAL-immunoassay detected an increased percentage of fucosylated PSA in patient serum with higher Gleason scores. Conclusion: We have developed quantitative lectin-immunoassays for serum fucosylated PSA. Our data demonstrated that fucosylated PSA-AAL, {\%} fucosylated PSA-AAL and fucosylated PSA-LCA levels could be effective biomarkers to differentiate aggressive prostate cancer [especially Gleason 7 (4 + 3) or above] from non-aggressive disease. We believe that application of these lectin-immunoassays to a larger patient population is needed to evaluate the clinical utilities of fucosylated PSA using AAL-PSA and LCA-PSA for aggressive prostate cancer.",
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AU - Sokoll, Lori J

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AU - Zhang, Zhen

AU - Zhang, Hui

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