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Theranostics 2021; 11(13):6214-6224. doi:10.7150/thno.55676 This issue Cite

Research Paper

A panel of selected serum protein biomarkers for the detection of aggressive prostate cancer

Jin Song^1*, Shiyong Ma^1*, Lori J. Sokoll^1,2,3, Rodrigo V. Eguez¹, Naseruddin Höti¹, Hui Zhang^1,2, Phaedre Mohr¹, Renu Dua¹, Dattatraya Patil⁵, Kristen Douglas May⁵, Sierra Williams⁵, Rebecca Arnold⁵, Martin G. Sanda⁵, Daniel W. Chan^1,2,3,4✉, Zhen Zhang^1,2✉

1. Center for Biomarker Discovery and Translation, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
2. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
3. Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
4. Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
5. Department of Urology, Emory University School of Medicine, Atlanta, GA, 30322, USA.
*These authors contributed equally to this work.

✉ Corresponding authors: contributed equally to this work. Daniel W. Chan, Department of Pathology, Johns Hopkins University School of Medicine, 1550 Orleans Street, Baltimore, MD 21231, USA. Tel: 410-955-2674; Fax: 443-287-6388; E-mail: dchanedu. Zhen Zhang, Department of Pathology, Johns Hopkins University School of Medicine, 1550 Orleans Street, Baltimore, MD 21231, USA. Tel: 410-502-7871; Fax: 443-287-6388; E-mail: zzhang7edu. More

Abstract

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.

Keywords: prostate, prostate neoplasms, prostate-specific antigen, biomarker, aggressive

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