Chemokine Markers Predict Biochemical Recurrence of Prostate Cancer following Prostatectomy

Department of Urologic Surgery, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37232, USA.
Clinical Cancer Research (Impact Factor: 8.72). 01/2009; 14(23):7790-7. DOI: 10.1158/1078-0432.CCR-08-1716
Source: PubMed


Stratifying patients who have a high risk of prostate cancer recurrence following prostatectomy can potentiate the use of adjuvant therapy at an early stage. Inflammation has emerged as a mediator of prostate cancer metastatic progression. We hypothesized that chemokines can be biomarkers for distinguishing patients with high risk for biochemical recurrence of prostate cancer.
In a nested case-control study, 82 subjects developed biochemical recurrence within 5 years of prostatectomy. Prostate tissues from 98 age-matched subjects who were recurrence-free following prostatectomy in the same period were the controls. A high-throughput lectin-based enrichment of prostate tissue enabled multiplex ELISA to identify the expression of three chemokines to discriminate the two patient populations.
The expression of CX3CL1 and IL-15 in prostate tissue was associated with 5-year biochemical recurrence-free survival following prostatectomy. However, the expression of chemokine ligand 4 (CCL4) was associated with biochemical recurrence. Multivariable logistic regression model combining preoperative prostate-specific antigen, Gleason score, surgical margin, and seminal vesicle status with the three chemokines doubled the specificity of prediction at 90% sensitivity compared with use of the clinicopathologic variables alone (P < 0.0001). Survival analysis yielded a nomogram that supported the use of CX3CL1, IL-15, and CCL4 in predicting 1-, 3-, and 5-year recurrence-free survival after prostatectomy.
Each of the three chemokines can serve as independent predictors of biochemical recurrence. However, the combination of chemokine biomarkers plus clinicopathologic variables discriminated prostatectomy subjects for the probability of biochemical recurrence significantly better than clinicopathologic variables alone.

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Available from: David Blum, Feb 13, 2014
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    • "Various approaches in improving the role of PSA in early prostate cancer detection have been tested, but their benefit to overall survival is yet to be proven [2], [3]. Ultimately, there is a subgroup of men without conventional negative factors harboring high risk, aggressive disease and are even at elevated risk of early recurrence after attempted definitive local therapy [4], [5], [6]. The ongoing challenge facing clinicians is how to identify this cohort of men at high risk, from the larger cohort of men who are likely harboring more indolent disease [7]. "
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    • "iological , pathological , and mo - lecular evidence have supported the idea that chronic inflammation is causally linked to prostate carcinogenesis ( Haverkamp et al . 2008 ; Klein and Silverman 2008 ; Bardia et al . 2009 ) . For example , expression of certain chemokines is a predictor of biochemical disease recurrence in human prostate cancer ( Blum et al . 2008 ) . Moreover , administration of the potent heterocyclic amine PhIP ( 2 - amino - 1 - methyl - 6 - phenyl - imidazo [ 4 , 5 - b ] pyridine ) , results in chronic inflam - mation and promotes prostatic hyperplasia and PIN in rodents ( Borowsky et al . 2006 ; Elkahwaji et al . 2007 ; Nakai et al . 2007 ; Elkahwaji et al . 2009 ; Khalili e"
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    Preview · Article · Sep 2010 · Genes & development
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    • "The β subunit gene, CCL4, was also differentially expressed in G4. CCL4 was recently reported to be associated with prostate cancer recurrence by Blum et al. [43]. "
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