Macrophage inhibitory cytokine 1: a new prognostic marker in prostate cancer.
OBJECTIVE
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.


METHODS
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.
Centre for Applied Medical Research, St. Vincent's Hospital and University of New South Wales, Sydney, Australia.
David A
DA
Brown
Fredrik
F
Lindmark
Pär
P
Stattin
Katarina
K
Bälter
Hans-Olov
HO
Adami
Sigun L
SL
Zheng
Jianfeng
J
Xu
William B
WB
Isaacs
Henrik
H
Grönberg
Samuel N
SN
Breit
Fredrik E
FE
Wiklund
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood* / Q000401:mortality / Q000628:therapy
D014408:Biomarkers, Tumor; D055436:Growth Differentiation Factor 15; D017430:Prostate-Specific Antigen