Macrophage inhibitory cytokine 1: A new prognostic marker in prostate cancer

David A. Brown, Fredrik Lindmark, Pär Stattin, Katarina Bälter, Hans Olov Adami, Sigun L. Zheng, Jianfeng Xu, William B. Isaacs, Henrik Grönberg, Samuel N. Breit, Fredrik E. Wiklund

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6658-6664
Number of pages7
JournalClinical Cancer Research
Volume15
Issue number21
DOIs
StatePublished - Nov 1 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Brown, D. A., Lindmark, F., Stattin, P., Bälter, K., Adami, H. O., Zheng, S. L., Xu, J., Isaacs, W. B., Grönberg, H., Breit, S. N., & Wiklund, F. E. (2009). Macrophage inhibitory cytokine 1: A new prognostic marker in prostate cancer. Clinical Cancer Research, 15(21), 6658-6664. https://doi.org/10.1158/1078-0432.CCR-08-3126