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A panel of selected serum protein biomarkers for the detection of aggressive prostate cancer
Background: Current PSA-based tests used to detect prostate cancer (PCa) lack sufficient specificity, leading to significant overdetection and overtreatment. Our previous studies showed that serum fucosylated PSA (Fuc-PSA) and soluble TEK receptor tyrosine kinase (Tie-2) had the ability to predict a...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120218/ https://www.ncbi.nlm.nih.gov/pubmed/33995654 http://dx.doi.org/10.7150/thno.55676 |
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author | Song, Jin Ma, Shiyong Sokoll, Lori J. Eguez, Rodrigo V. Höti, Naseruddin Zhang, Hui Mohr, Phaedre Dua, Renu Patil, Dattatraya May, Kristen Douglas Williams, Sierra Arnold, Rebecca Sanda, Martin G. Chan, Daniel W. Zhang, Zhen |
author_facet | Song, Jin Ma, Shiyong Sokoll, Lori J. Eguez, Rodrigo V. Höti, Naseruddin Zhang, Hui Mohr, Phaedre Dua, Renu Patil, Dattatraya May, Kristen Douglas Williams, Sierra Arnold, Rebecca Sanda, Martin G. Chan, Daniel W. Zhang, Zhen |
author_sort | Song, Jin |
collection | PubMed |
description | Background: Current PSA-based tests used to detect prostate cancer (PCa) lack sufficient specificity, leading to significant overdetection and overtreatment. Our previous studies showed that serum fucosylated PSA (Fuc-PSA) and soluble TEK receptor tyrosine kinase (Tie-2) had the ability to predict aggressive (AG) PCa. Additional biomarkers are needed to address this significant clinical problem. Methods: A comprehensive Pubmed search followed by multiplex immunoassays identified candidate biomarkers associated with AG PCa. Subsequently, multiplex and lectin-based immunoassays were applied to a case-control set of sera from subjects with AG PCa, low risk PCa, and non-PCa (biopsy negative). These candidate biomarkers were further evaluated for their ability as panels to complement the prostate health index (phi) in detecting AG PCa. Results: When combined through logistic regression, two panel of biomarkers achieved the best performance: 1) phi, Fuc-PSA, SDC1, and GDF-15 for the detection of AG from low risk PCa and 2) phi, Fuc-PSA, SDC1, and Tie-2 for the detection of AG from low risk PCa and non-PCa, with noticeable improvements in ROC analysis over phi alone (AUCs: 0.942 vs 0.872, and 0.934 vs 0.898, respectively). At a fixed sensitivity of 95%, the panels improved specificity with statistical significance in detecting AG from low risk PCa (76.0% vs 56%, p=0.029), and from low risk PCa and non-PCa (78.2% vs 65.5%, p=0.010). Conclusions: Multivariate panels of serum biomarkers identified in this study demonstrated clinically meaningful improvement over the performance of phi, and warrant further clinical validation, which may contribute to the management of PCa. |
format | Online Article Text |
id | pubmed-8120218 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-81202182021-05-15 A panel of selected serum protein biomarkers for the detection of aggressive prostate cancer Song, Jin Ma, Shiyong Sokoll, Lori J. Eguez, Rodrigo V. Höti, Naseruddin Zhang, Hui Mohr, Phaedre Dua, Renu Patil, Dattatraya May, Kristen Douglas Williams, Sierra Arnold, Rebecca Sanda, Martin G. Chan, Daniel W. Zhang, Zhen Theranostics Research Paper Background: Current PSA-based tests used to detect prostate cancer (PCa) lack sufficient specificity, leading to significant overdetection and overtreatment. Our previous studies showed that serum fucosylated PSA (Fuc-PSA) and soluble TEK receptor tyrosine kinase (Tie-2) had the ability to predict aggressive (AG) PCa. Additional biomarkers are needed to address this significant clinical problem. Methods: A comprehensive Pubmed search followed by multiplex immunoassays identified candidate biomarkers associated with AG PCa. Subsequently, multiplex and lectin-based immunoassays were applied to a case-control set of sera from subjects with AG PCa, low risk PCa, and non-PCa (biopsy negative). These candidate biomarkers were further evaluated for their ability as panels to complement the prostate health index (phi) in detecting AG PCa. Results: When combined through logistic regression, two panel of biomarkers achieved the best performance: 1) phi, Fuc-PSA, SDC1, and GDF-15 for the detection of AG from low risk PCa and 2) phi, Fuc-PSA, SDC1, and Tie-2 for the detection of AG from low risk PCa and non-PCa, with noticeable improvements in ROC analysis over phi alone (AUCs: 0.942 vs 0.872, and 0.934 vs 0.898, respectively). At a fixed sensitivity of 95%, the panels improved specificity with statistical significance in detecting AG from low risk PCa (76.0% vs 56%, p=0.029), and from low risk PCa and non-PCa (78.2% vs 65.5%, p=0.010). Conclusions: Multivariate panels of serum biomarkers identified in this study demonstrated clinically meaningful improvement over the performance of phi, and warrant further clinical validation, which may contribute to the management of PCa. Ivyspring International Publisher 2021-04-15 /pmc/articles/PMC8120218/ /pubmed/33995654 http://dx.doi.org/10.7150/thno.55676 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Song, Jin Ma, Shiyong Sokoll, Lori J. Eguez, Rodrigo V. Höti, Naseruddin Zhang, Hui Mohr, Phaedre Dua, Renu Patil, Dattatraya May, Kristen Douglas Williams, Sierra Arnold, Rebecca Sanda, Martin G. Chan, Daniel W. Zhang, Zhen A panel of selected serum protein biomarkers for the detection of aggressive prostate cancer |
title | A panel of selected serum protein biomarkers for the detection of aggressive prostate cancer |
title_full | A panel of selected serum protein biomarkers for the detection of aggressive prostate cancer |
title_fullStr | A panel of selected serum protein biomarkers for the detection of aggressive prostate cancer |
title_full_unstemmed | A panel of selected serum protein biomarkers for the detection of aggressive prostate cancer |
title_short | A panel of selected serum protein biomarkers for the detection of aggressive prostate cancer |
title_sort | panel of selected serum protein biomarkers for the detection of aggressive prostate cancer |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120218/ https://www.ncbi.nlm.nih.gov/pubmed/33995654 http://dx.doi.org/10.7150/thno.55676 |
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