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


<b>Background:</b> 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. <b>Methods:</b> 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 (<i>phi</i>) in detecting AG PCa. <b>Results:</b> When combined through logistic regression, two panel of biomarkers achieved the best performance: 1) <i>phi,</i> Fuc-PSA, SDC1, and GDF-15 for the detection of AG from low risk PCa and 2) <i>phi</i>, 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 <i>phi</i> 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%, <i>p</i>=0.029), and from low risk PCa and non-PCa (78.2% vs 65.5%, <i>p</i>=0.010). <b>Conclusions:</b> Multivariate panels of serum biomarkers identified in this study demonstrated clinically meaningful improvement over the performance of <i>phi</i>, and warrant further clinical validation, which may contribute to the management of PCa.

  • Arnold R
  • Chan DW
  • Dua R
  • Eguez RV
  • Höti N
  • Ma S
  • May KD
  • Mohr P
  • Patil D
  • Sanda MG
  • Sokoll LJ
  • Song J
  • Williams S
  • Zhang H
  • Zhang Z
PubMed ID
Appears In
Theranostics, 2021, 11 (13)