Article

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: 8.19). 01/2009; 14(23):7790-7. DOI: 10.1158/1078-0432.CCR-08-1716
Source: PubMed

ABSTRACT 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.

Download full-text

Full-text

Available from: David Blum, Feb 13, 2014
0 Followers
 · 
113 Views
  • Source
    • "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"
    [Show abstract] [Hide abstract]
    ABSTRACT: Despite much recent progress, prostate cancer continues to represent a major cause of cancer-related mortality and morbidity in men. Since early studies on the role of the androgen receptor that led to the advent of androgen deprivation therapy in the 1940s, there has long been intensive interest in the basic mechanisms underlying prostate cancer initiation and progression, as well as the potential to target these processes for therapeutic intervention. Here, we present an overview of major themes in prostate cancer research, focusing on current knowledge of principal events in cancer initiation and progression. We discuss recent advances, including new insights into the mechanisms of castration resistance, identification of stem cells and tumor-initiating cells, and development of mouse models for preclinical evaluation of novel therapuetics. Overall, we highlight the tremendous research progress made in recent years, and underscore the challenges that lie ahead.
    Genes & development 09/2010; 24(18):1967-2000. DOI:10.1101/gad.1965810 · 12.64 Impact Factor
  • Source
    • "Chemokine expression profiles have been shown to predict recurrence and disease free survival in many non-melanoma cancers. In prostate cancer, one study shows CX3CL1 and IL-15 expression in prostate tissue were associated with recurrence-free survival following prostatectomy, while CCL4 expression was associated with recurrence (Blum et al., 2008). Another study examining cancer cell expression of the receptor for CX3CL1, CX3CR1, shows that high expression of CX3CR1 in pancreatic ductal adenocarcinoma is associated with neurotropism of these cancer cells, likely due to the expression of CX3CL1 by neurons (Marchesi et al., 2008). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Chemokine ligand/receptor interactions affect melanoma cell growth, stimulate or inhibit angiogenesis, recruit leukocytes, promote metastasis, and alter the gene expression profile of the melanoma associated fibroblasts. Chemokine/chemokine receptor interactions can protect against tumor development/growth or can stimulate melanoma tumor progression, tumor growth and metastasis. Metastatic melanoma cells express chemokine receptors that play a major role in the specifying the organ site for metastasis, based upon receptor detection of the chemokine gradient elaborated by a specific organ/tissue. A therapeutic approach that utilizes the protective benefit of chemokines involves delivery of angiostatic chemokines or chemokines that stimulate the infiltration of cytotoxic T cells and natural killer T cells into the tumor microenvironment. An alternative approach that tackles the tumorigenic property of chemokines uses chemokine antibodies or chemokine receptor antagonists to target the growth and metastatic properties of these interactions. Based upon our current understanding of the role of chemokine-mediated inflammation in cancer, it is important that we learn to appropriately regulate the chemokine contribution to the tumorigenic 'cytokine/chemokine storm', and to metastasis.
    Pigment Cell & Melanoma Research 03/2009; 22(2):175-86. DOI:10.1111/j.1755-148X.2009.00554.x · 5.64 Impact Factor
Show more