Macrophage Inhibitory Cytokine 1: A New Prognostic Marker in Prostate Cancer

Purpose: High serum levels of macrophage inhibitory cytokine 1 (MIC-1) are strongly associated with metastatic prostate cancer, suggesting MIC-1 is a biomarker for prostate cancer prognosis. Experimental Design: We conducted a prospective cohort study of 1,442 Swedish men with a pathologically verified diagnosis of prostate cancer between 2001 and 2003. Blood was drawn either pretreatment (n = 431) or posttreatment (n = 1,011) and cases were followed for a mean time of 4.9 years (range, 0.1-6.8 years). Results: MIC-1 serum levels independently predicted poor cancer-specific survival with an almost 3-fold higher cancer death rate in patients with serum levels in the highest quartile compared with men with serum levels in the lowest quartile (adjusted hazard ratio, 2.98; 95% confidence interval, 1.82-4.68). Pretreatment MIC-1 levels revealed an even stronger association with disease outcome with an 8-fold higher death rate in the highest compared with the lowest category (adjusted hazard ratio, 7.98; 95% confidence interval, 1.73-36.86). Among patients considered to have localized disease, MIC-1 significantly increased the discriminative capacity between indolent and lethal prostate cancer compared with the established prognostic markers clinical stage, pathologic grade, and prostate-specific antigen level (P = 0.016). A sequence variant in the MIC-1 gene was associated with decreased MIC-1 serum levels (P = 0.002) and decreased prostate cancer mortality (P = 0.003), suggesting a causative role of MIC-1 in prostate cancer prognosis. Conclusions: Serum MIC-1 concentration is a novel biomarker capable of predicting prostate cancer prognosis. (Clin Cancer Res 2009;15(21):6658–64)

[1]  Katja Fall,et al.  Reliability of death certificates in prostate cancer patients , 2008, Scandinavian journal of urology and nephrology.

[2]  W. D. Fairlie,et al.  Tumor-induced anorexia and weight loss are mediated by the TGF-β superfamily cytokine MIC-1 , 2007, Nature Medicine.

[3]  C. Bermejo,et al.  Management of the complications of radical prostatectomy , 2007, Current urology reports.

[4]  L. Holmberg,et al.  Prostate-specific antigen levels as a predictor of lethal prostate cancer. , 2007, Journal of the National Cancer Institute.

[5]  A. Jukkola-Vuorinen,et al.  Serum Macrophage Inhibitory Cytokine-1 Concentrations Correlate with the Presence of Prostate Cancer Bone Metastases , 2007, Cancer Epidemiology Biomarkers & Prevention.

[6]  C. Bermejo,et al.  Management of the complications of radical prostatectomy , 2007 .

[7]  H. Johnen,et al.  Role of macrophage inhibitory cytokine-1 in tumorigenesis and diagnosis of cancer. , 2006, Cancer research.

[8]  G. Hampton,et al.  Measurement of Serum Levels of Macrophage Inhibitory Cytokine 1 Combined with Prostate-Specific Antigen Improves Prostate Cancer Diagnosis , 2006, Clinical Cancer Research.

[9]  Ulrich Pfeffer,et al.  The Transforming Growth Factor-β Family Members Bone Morphogenetic Protein-2 and Macrophage Inhibitory Cytokine-1 as Mediators of the Antiangiogenic Activity of N-(4-Hydroxyphenyl)Retinamide , 2005, Clinical Cancer Research.

[10]  James A Hanley,et al.  20-year outcomes following conservative management of clinically localized prostate cancer. , 2005, JAMA.

[11]  L. Holmberg,et al.  The National Prostate Cancer Register in Sweden 1998—2002: Trends in incidence, treatment and survival , 2005, Scandinavian journal of urology and nephrology.

[12]  J. Kench,et al.  The propeptide mediates formation of stromal stores of PROMIC-1: role in determining prostate cancer outcome. , 2005, Cancer research.

[13]  L. Klotz Active surveillance with selective delayed intervention: walking the line between overtreatment for indolent disease and undertreatment for aggressive disease. , 2005, The Canadian journal of urology.

[14]  Mark Daly,et al.  Haploview: analysis and visualization of LD and haplotype maps , 2005, Bioinform..

[15]  G. Chodak,et al.  Natural history of early localized prostate cancer. , 2004, JAMA.

[16]  Jaime Pujadas Oláno,et al.  Natural history of early localized prostate cancer. , 2004, JAMA.

[17]  Pär Stattin,et al.  H6D polymorphism in macrophage-inhibitory cytokine-1 gene associated with prostate cancer. , 2004, Journal of the National Cancer Institute.

[18]  K. Song,et al.  Macrophage inhibitory cytokine-1 induces the invasiveness of gastric cancer cells by up-regulating the urokinase-type plasminogen activator system. , 2003, Cancer research.

[19]  T. Nakamura,et al.  Quantitative analysis of macrophage inhibitory cytokine-1 (MIC-1) gene expression in human prostatic tissues , 2003, British Journal of Cancer.

[20]  J. Welsh,et al.  Large-scale delineation of secreted protein biomarkers overexpressed in cancer tissue and serum , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[21]  L. Demers,et al.  Biochemical markers and skeletal metastases. , 2001, Clinical orthopaedics and related research.

[22]  S. Breit,et al.  Antibody-based approach to high-volume genotyping for MIC-1 polymorphism. , 2002, BioTechniques.

[23]  Erwin G. Van Meir,et al.  Anoxia induces macrophage inhibitory cytokine-1 (MIC-1) in glioblastoma cells independently of p53 and HIF-1 , 2002, Oncogene.

[24]  S. Baek,et al.  Cyclooxygenase inhibitors regulate the expression of a TGF-beta superfamily member that has proapoptotic and antitumorigenic activities. , 2001, Molecular pharmacology.

[25]  E. Bergstralh,et al.  Use of Gleason score, prostate specific antigen, seminal vesicle and margin status to predict biochemical failure after radical prostatectomy. , 2001, The Journal of urology.

[26]  C. Arrowsmith,et al.  Placental Transforming Growth Factor-β Is a Downstream Mediator of the Growth Arrest and Apoptotic Response of Tumor Cells to DNA Damage and p53 Overexpression* , 2000, The Journal of Biological Chemistry.

[27]  C. de la Piedra,et al.  Aminoterminal propeptide of type I collagen and bone alkaline phosphatase in the study of bone metastases associated with prostatic carcinoma. , 1999, Scandinavian journal of clinical and laboratory investigation.

[28]  M. Kattan,et al.  A preoperative nomogram for disease recurrence following radical prostatectomy for prostate cancer. , 1998, Journal of the National Cancer Institute.

[29]  H. Lilja,et al.  Dual-label one-step immunoassay for simultaneous measurement of free and total prostate-specific antigen concentrations and ratios in serum. , 1995, Clinical chemistry.

[30]  F. Marshall,et al.  Selection of men at high risk for disease recurrence for experimental adjuvant therapy following radical prostatectomy. , 1995, Urology.

[31]  R. Gray A Class of $K$-Sample Tests for Comparing the Cumulative Incidence of a Competing Risk , 1988 .

[32]  J. Hanley,et al.  A method of comparing the areas under receiver operating characteristic curves derived from the same cases. , 1983, Radiology.