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

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 c...

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Main Authors: Ce Wang, Naseruddin Höti, Tung-Shing Mamie Lih, Lori J. Sokoll, Rui Zhang, Zhen Zhang, Hui Zhang, Daniel W. Chan
Format: Article
Language:English
Published: BMC 2019-04-01
Series:Clinical Proteomics
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12014-019-9234-4
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author Ce Wang
Naseruddin Höti
Tung-Shing Mamie Lih
Lori J. Sokoll
Rui Zhang
Zhen Zhang
Hui Zhang
Daniel W. Chan
author_facet Ce Wang
Naseruddin Höti
Tung-Shing Mamie Lih
Lori J. Sokoll
Rui Zhang
Zhen Zhang
Hui Zhang
Daniel W. Chan
author_sort Ce Wang
collection DOAJ
description 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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spelling doaj.art-0414eb87a33c4689b53d02b5c22d42c02022-12-21T17:25:28ZengBMCClinical Proteomics1542-64161559-02752019-04-011611810.1186/s12014-019-9234-4Development of a glycoproteomic strategy to detect more aggressive prostate cancer using lectin-immunoassays for serum fucosylated PSACe Wang0Naseruddin Höti1Tung-Shing Mamie Lih2Lori J. Sokoll3Rui Zhang4Zhen Zhang5Hui Zhang6Daniel W. Chan7Department of Pathology, Johns Hopkins MedicineDepartment of Pathology, Johns Hopkins MedicineDepartment of Pathology, Johns Hopkins MedicineDepartment of Pathology, Johns Hopkins MedicineDepartment of Pathology, Johns Hopkins MedicineDepartment of Pathology, Johns Hopkins MedicineDepartment of Pathology, Johns Hopkins MedicineDepartment of Pathology, Johns Hopkins MedicineAbstract 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.http://link.springer.com/article/10.1186/s12014-019-9234-4Lectin-immunoassaysGlycoproteomicFucosylated PSAProstate cancer
spellingShingle Ce Wang
Naseruddin Höti
Tung-Shing Mamie Lih
Lori J. Sokoll
Rui Zhang
Zhen Zhang
Hui Zhang
Daniel W. Chan
Development of a glycoproteomic strategy to detect more aggressive prostate cancer using lectin-immunoassays for serum fucosylated PSA
Clinical Proteomics
Lectin-immunoassays
Glycoproteomic
Fucosylated PSA
Prostate cancer
title Development of a glycoproteomic strategy to detect more aggressive prostate cancer using lectin-immunoassays for serum fucosylated PSA
title_full Development of a glycoproteomic strategy to detect more aggressive prostate cancer using lectin-immunoassays for serum fucosylated PSA
title_fullStr Development of a glycoproteomic strategy to detect more aggressive prostate cancer using lectin-immunoassays for serum fucosylated PSA
title_full_unstemmed Development of a glycoproteomic strategy to detect more aggressive prostate cancer using lectin-immunoassays for serum fucosylated PSA
title_short Development of a glycoproteomic strategy to detect more aggressive prostate cancer using lectin-immunoassays for serum fucosylated PSA
title_sort development of a glycoproteomic strategy to detect more aggressive prostate cancer using lectin immunoassays for serum fucosylated psa
topic Lectin-immunoassays
Glycoproteomic
Fucosylated PSA
Prostate cancer
url http://link.springer.com/article/10.1186/s12014-019-9234-4
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