Large-scale independent validation of the nuclear factor-kappa B p65 prognostic biomarker in prostate cancer

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...

Celý popis

Uložené v:
Podrobná bibliografia
Vydané v:European journal of cancer (1990) Ročník 49; číslo 10; s. 2441 - 2448
Hlavní autori: 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
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: Kidlington Elsevier Ltd 01.07.2013
Elsevier
Predmet:
Aged
Biochemical recurrence
Biological and medical sciences
Biological marker
Biomarkers, Tumor - analysis
Cell Nucleus - metabolism
Cohort Studies
Disease Progression
Disease-Free Survival
Hematology, Oncology and Palliative Medicine
Humans
Immunohistochemistry
Immunohistochemistry - statistics & numerical data
Male
Medical sciences
Middle Aged
Multiple tumors. Solid tumors. Tumors in childhood (general aspects)
Multivariate Analysis
Neoplasm Recurrence, Local
Nuclear factor-kappa B (NF-κB)
Pharmacology. Drug treatments
Prognosis
Proportional Hazards Models
Prostate - metabolism
Prostate - pathology
Prostate - surgery
Prostate-Specific Antigen - analysis
Prostatectomy - methods
Prostatic Neoplasms - diagnosis
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - surgery
Seminal Vesicles - metabolism
Seminal Vesicles - pathology
Sensitivity and Specificity
Severity of Illness Index
Tissue Array Analysis - statistics & numerical data
Transcription Factor RelA - analysis
Tumors
Immunohistochemistry
Biological marker
Nuclear factor-kappa B (NF-κB)
Biochemical recurrence
Validation
Urinary system disease
Prognosis
Prostate disease
Malignant tumor
Anatomic pathology
Cancerology
Transcription factor NFκB
Male genital diseases
Prostate cancer
Cancer
ISSN:0959-8049, 1879-0852, 1879-0852
On-line prístup:Získať plný text
Tagy: Pridať tag
Žiadne tagy, Buďte prvý, kto otaguje tento záznam!
Popis
Shrnutí: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. 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. 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. 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.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0959-8049
1879-0852
1879-0852
DOI:10.1016/j.ejca.2013.02.026