Large-scale independent validation of the nuclear factor-kappa B p65 prognostic biomarker in prostate cancer
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Large-scale independent validation of the nuclear factor-kappa B p65 prognostic biomarker in prostate cancer. / Gannon, Philippe O; Lessard, Laurent; Stevens, Louis-Mathieu; Forest, Valérie; Bégin, Louis R; Minner, Sarah; Tennstedt, Pierre; Schlomm, Thorsten; Mes-Masson, Anne-Marie; Saad, Fred.
in: EUR J CANCER, Jahrgang 49, Nr. 10, 01.07.2013, S. 2441-8.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Large-scale independent validation of the nuclear factor-kappa B p65 prognostic biomarker in prostate cancer
AU - Gannon, Philippe O
AU - Lessard, Laurent
AU - Stevens, Louis-Mathieu
AU - Forest, Valérie
AU - Bégin, Louis R
AU - Minner, Sarah
AU - Tennstedt, Pierre
AU - Schlomm, Thorsten
AU - Mes-Masson, Anne-Marie
AU - Saad, Fred
N1 - Copyright © 2013 Elsevier Ltd. All rights reserved.
PY - 2013/7/1
Y1 - 2013/7/1
N2 - PURPOSE: Over the last decade, we and others have uncovered a robust association between the nuclear localisation of nuclear factor-kappa B (NF-κB) p65, prostate cancer (PCa) aggressiveness and biochemical recurrence (BCR). Our goal was to validate these results in a large independent cohort of PCa patients who underwent radical prostatectomy.EXPERIMENTAL DESIGN: A set of 1826 fully annotated prostate cancers treated by radical prostatectomy were analysed in a tissue microarray (TMA) format for NF-κB p65 immunohistochemistry-based protein expression. We performed standard Cox proportional hazard regression models for follow-up data, bootstrap procedure for model internal validation, Harrell's concordance index for model discrimination and graphical assessment of predicted versus actual outcomes for model calibration.RESULTS: We observed a significant association between an increase in the nuclear frequency of NF-κB p65 and Gleason score (P<0.001), overall BCR (P<0.001) and development of metastases (P=0.001). NF-κB was found to be an independent predictor of BCR (P<0.001, Cox regression). However its contribution to the predictive accuracy of a multivariate model, which included preoperative PSA, Gleason score, extraprostatic extension, lymph node invasion, seminal vesicle involvement and surgical margin status, was modest.CONCLUSIONS: Our study offers validating results linking NF-κB p65 with disease progression using a large cohort of European men. However, the contribution of NF-κB to a post-surgical predictive model appears modest. Further validating work should focus on evaluating the contribution of NF-κB p65 in pre-treatment models.
AB - PURPOSE: Over the last decade, we and others have uncovered a robust association between the nuclear localisation of nuclear factor-kappa B (NF-κB) p65, prostate cancer (PCa) aggressiveness and biochemical recurrence (BCR). Our goal was to validate these results in a large independent cohort of PCa patients who underwent radical prostatectomy.EXPERIMENTAL DESIGN: A set of 1826 fully annotated prostate cancers treated by radical prostatectomy were analysed in a tissue microarray (TMA) format for NF-κB p65 immunohistochemistry-based protein expression. We performed standard Cox proportional hazard regression models for follow-up data, bootstrap procedure for model internal validation, Harrell's concordance index for model discrimination and graphical assessment of predicted versus actual outcomes for model calibration.RESULTS: We observed a significant association between an increase in the nuclear frequency of NF-κB p65 and Gleason score (P<0.001), overall BCR (P<0.001) and development of metastases (P=0.001). NF-κB was found to be an independent predictor of BCR (P<0.001, Cox regression). However its contribution to the predictive accuracy of a multivariate model, which included preoperative PSA, Gleason score, extraprostatic extension, lymph node invasion, seminal vesicle involvement and surgical margin status, was modest.CONCLUSIONS: Our study offers validating results linking NF-κB p65 with disease progression using a large cohort of European men. However, the contribution of NF-κB to a post-surgical predictive model appears modest. Further validating work should focus on evaluating the contribution of NF-κB p65 in pre-treatment models.
KW - Aged
KW - Cell Nucleus
KW - Cohort Studies
KW - Disease Progression
KW - Disease-Free Survival
KW - Humans
KW - Immunohistochemistry
KW - Male
KW - Middle Aged
KW - Multivariate Analysis
KW - Neoplasm Recurrence, Local
KW - Prognosis
KW - Proportional Hazards Models
KW - Prostate
KW - Prostate-Specific Antigen
KW - Prostatectomy
KW - Prostatic Neoplasms
KW - Seminal Vesicles
KW - Sensitivity and Specificity
KW - Severity of Illness Index
KW - Tissue Array Analysis
KW - Transcription Factor RelA
KW - Tumor Markers, Biological
U2 - 10.1016/j.ejca.2013.02.026
DO - 10.1016/j.ejca.2013.02.026
M3 - SCORING: Journal article
C2 - 23541563
VL - 49
SP - 2441
EP - 2448
JO - EUR J CANCER
JF - EUR J CANCER
SN - 0959-8049
IS - 10
ER -