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

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Growth Differentiation Factor 15
Prostatic Neoplasms
Serum
Biomarkers
Mortality
Confidence Intervals
Prostate-Specific Antigen
Neoplasms
Cohort Studies
Research Design

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Brown, D. A., Lindmark, F., Stattin, P., Bälter, K., Adami, H. O., Zheng, S. L., ... 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

Macrophage inhibitory cytokine 1 : A new prognostic marker in prostate cancer. / Brown, David A.; Lindmark, Fredrik; Stattin, Pär; Bälter, Katarina; Adami, Hans Olov; Zheng, Sigun L.; Xu, Jianfeng; Isaacs, William B; Grönberg, Henrik; Breit, Samuel N.; Wiklund, Fredrik E.

In: Clinical Cancer Research, Vol. 15, No. 21, 01.11.2009, p. 6658-6664.

Research output: Contribution to journalArticle

Brown, DA, Lindmark, F, Stattin, P, Bälter, K, Adami, HO, Zheng, SL, Xu, J, Isaacs, WB, Grönberg, H, Breit, SN & Wiklund, FE 2009, 'Macrophage inhibitory cytokine 1: A new prognostic marker in prostate cancer', Clinical Cancer Research, vol. 15, no. 21, pp. 6658-6664. https://doi.org/10.1158/1078-0432.CCR-08-3126
Brown DA, Lindmark F, Stattin P, Bälter K, Adami HO, Zheng SL et al. Macrophage inhibitory cytokine 1: A new prognostic marker in prostate cancer. Clinical Cancer Research. 2009 Nov 1;15(21):6658-6664. https://doi.org/10.1158/1078-0432.CCR-08-3126
Brown, David A. ; Lindmark, Fredrik ; Stattin, Pär ; Bälter, Katarina ; Adami, Hans Olov ; Zheng, Sigun L. ; Xu, Jianfeng ; Isaacs, William B ; Grönberg, Henrik ; Breit, Samuel N. ; Wiklund, Fredrik E. / Macrophage inhibitory cytokine 1 : A new prognostic marker in prostate cancer. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 21. pp. 6658-6664.
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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.",
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T2 - A new prognostic marker in prostate cancer

AU - Brown, David A.

AU - Lindmark, Fredrik

AU - Stattin, Pär

AU - Bälter, Katarina

AU - Adami, Hans Olov

AU - Zheng, Sigun L.

AU - Xu, Jianfeng

AU - Isaacs, William B

AU - Grönberg, Henrik

AU - Breit, Samuel N.

AU - Wiklund, Fredrik E.

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N2 - 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.

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