The identification and internal validation of a preoperative serum biomarker panel to determine extracapsular extension in patients with prostate cancer

Authors

  • Sheng F. Oon,

    Corresponding author
    1. UCD School of Medicine and Medical Science, Dublin, Ireland
    2. UCD Conway Institute of Biomolecular and Biomedical Science, Dublin, Ireland
    • UCD Conway Institute, School of Medicine and Medical Science, Belfield, University College Dublin, Dublin 4, Ireland.
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  • Deirdre M. Fanning,

    1. UCD School of Medicine and Medical Science, Dublin, Ireland
    2. UCD Conway Institute of Biomolecular and Biomedical Science, Dublin, Ireland
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  • Yue Fan,

    1. UCD School of Medicine and Medical Science, Dublin, Ireland
    2. UCD Conway Institute of Biomolecular and Biomedical Science, Dublin, Ireland
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  • Susie Boyce,

    1. UCD School of Medicine and Medical Science, Dublin, Ireland
    2. UCD Conway Institute of Biomolecular and Biomedical Science, Dublin, Ireland
    3. UCD School of Mathematical Sciences, Dublin, Ireland
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  • T. Brendan Murphy,

    1. UCD School of Mathematical Sciences, Dublin, Ireland
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  • John M. Fitzpatrick,

    1. UCD School of Medicine and Medical Science, Dublin, Ireland
    2. Department of Urology, Mater Misericordae Universty Hospital, Dublin, Ireland
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  • R. William Watson

    1. UCD School of Medicine and Medical Science, Dublin, Ireland
    2. UCD Conway Institute of Biomolecular and Biomedical Science, Dublin, Ireland
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  • Sheng F. Oon and Deirdre M. Fanning contributed equally to this work.

  • Disclosure Statement: The authors Sheng-Fei Oon, Deirdre Fanning, Yue Fan, Susie Boyce, T. Brendan Murphy and R. William Watson have no relevant financial or other beneficial interests to disclose. John M. Fitzpatrick is a consultant and lecturer (“A” grade relation) to Sanofi-Aventis, Glaxo Smith Kline, Orion, Millenium, Aventis and Janssen and has received financial compensation for his consultations and services in the past.

Abstract

BACKGROUND

Accurate preoperative staging of prostate cancer (PCa) is important but current diagnostic methods cannot accurately determine extracapsular extension (ECE), resulting in the possible triage of patients towards a less appropriate arm of therapy. This has consequences to patient care and better methods of preoperatively determining ECE are required.

METHODS

We followed a biomarker development pathway and compared the preoperative serum expressions of VEGF-D, PEDF, IGF-I, IGFBP3, and CD14 in patients from the Irish Prostate Cancer Research Consortium (PCRC) with radical prostatectomy determined ECE against patients with nonECE.

RESULTS

The expression measurements of five proteins were fitted into a logistic regression model and backwards variable elimination methods were applied which resulted in a model with IGFBP3 and CD14 as the best combination biomarker panel. This panel was tested in an independent cohort of patients using an optimized multiplex electrochemiluminescence assay. Receiver operating characteristic curves were generated and the areas under the curve (AUC) were calculated as an estimation of prediction accuracy. The biomarker panel was validated with an AUC of 76.6%, and a sensitivity and specificity of 80% and 75% was obtained.

CONCLUSIONS

This is the first internally validated, preoperative serum biomarker panel that identifies ECE in patients with Gleason score 7 PCa with AUC 76.6%. The panel surpasses the routinely used diagnostic standards in accuracy and may help to improve preoperative cancer staging, better inform treatment options, and improve the referral patterns of patients with urgently treatable cancers towards more appropriate arms of therapy. Prostate 72:1523–1531, 2012. © 2012 Wiley Periodicals, Inc.

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