Sheng F. Oon and Deirdre M. Fanning contributed equally to this work.
Version of Record online: 13 MAR 2012
Copyright © 2012 Wiley Periodicals, Inc.
Volume 72, Issue 14, pages 1523–1531, 1 October 2012
How to Cite
Oon, S. F., Fanning, D. M., Fan, Y., Boyce, S., Murphy, T. B., Fitzpatrick, J. M. and Watson, R. W. (2012), The identification and internal validation of a preoperative serum biomarker panel to determine extracapsular extension in patients with prostate cancer. Prostate, 72: 1523–1531. doi: 10.1002/pros.22506
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.
- Issue online: 24 AUG 2012
- Version of Record online: 13 MAR 2012
- Manuscript Accepted: 7 FEB 2012
- Manuscript Received: 8 JAN 2012
- Irish Cancer Society
- Royal College of Surgeons in Ireland
- British Urological Foundation
- HRB-SFI Translational Award 2010. Grant Number: TRA/2010/18
- Wellcome Trust-HRB Dublin Centre for Clinical Research
- prostate cancer;
- extracapsular extension
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.
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.
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.
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.