Serum Macrophage Inhibitory Cytokine-1 Concentrations Correlate with the Presence of Prostate Cancer Bone Metastases

Macrophage-inhibitory cytokine-1 (MIC-1) is a divergent member of the transforming growth factor β superfamily. It is up-regulated by nonsteroidal anti-inflammatory drugs and is highly expressed in human prostate cancer leading to high serum MIC-1 concentrations with advanced disease. A role for MIC...

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Published in:Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2007-03, Vol.16 (3), p.532-537
Main Authors: Selander, Katri S, Brown, David A, Sequeiros, Guillermo Blanco, Hunter, Mark, Desmond, Renee, Parpala, Teija, Risteli, Juha, Breit, Samuel N, Jukkola-Vuorinen, Arja
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Biological and medical sciences
Biomarkers, Tumor - blood
Bone metastases
Bone Neoplasms - blood
Bone Neoplasms - secondary
Cytokines - blood
Discriminant Analysis
Enzyme-Linked Immunosorbent Assay
Growth Differentiation Factor 15
Humans
Logistic Models
Male
Medical sciences
Metastasis/metastasis genes/metastasis models
MIC-1
Middle Aged
Nephrology. Urinary tract diseases
Organ sites and tumor types
Prostate cancer
Prostate-Specific Antigen - blood
Prostatic Neoplasms - blood
Prostatic Neoplasms - pathology
Retrospective Studies
ROC Curve
Tumor markers and detection of metastasis
Tumors
Tumors of the urinary system
Urinary tract. Prostate gland
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Summary:Macrophage-inhibitory cytokine-1 (MIC-1) is a divergent member of the transforming growth factor β superfamily. It is up-regulated by nonsteroidal anti-inflammatory drugs and is highly expressed in human prostate cancer leading to high serum MIC-1 concentrations with advanced disease. A role for MIC-1 has been implicated in the process of early bone formation, suggesting that it may also mediate sclerosis at the site of prostate cancer bone metastases. Consequently, the aim of this study was to retrospectively determine the relationship of serum MIC-1 concentration and other markers related to current and future prostate cancer bone metastasis in a cohort of 159 patients with prostate cancer. Serum markers included cross-linked carboxy-terminal telopeptide of type I collagen, prostate-specific antigen, and amino-terminal propeptide of type I procollagen (PINP). The mean values of all the biomarkers studied were significantly higher in patients with baseline bone metastases (BM+, n = 35), when compared with those without bone metastases (BM−, n = 124). In a multivariate logistic model, both MIC-1 and PINP independently predicted the presence of baseline bone metastasis. Based on receiver operator curve analysis, the best predictor for the presence of baseline bone metastasis was MIC-1, which was significantly better than carboxy-terminal telopeptide of type I collagen, prostate-specific antigen, and PINP. Patients who experienced bone relapse had significantly higher levels of baseline MIC-1 compared with patients who did not (1476.7 versus 988.4; P = 0.03). Current use of acetylsalicylic acid did not influence serum MIC-1 levels in this cohort. Although requiring validation prospectively, these results suggest that serum MIC-1 determination may be a valuable tool for the diagnosis of current and future bone metastases in patients with prostate cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(3):532–7)
ISSN:1055-9965
1538-7755
DOI:10.1158/1055-9965.EPI-06-0841