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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BMC
2019-04-01
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Series: | Clinical Proteomics |
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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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