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

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.

Plasma MIC-1 correlates with systemic inflammation but is not an independent determinant of nutritional status or survival in oesophago-gastric cancer

“…Abbreviations: CI ¼ confidence interval; CRP ¼ C-reactive protein; mGPS ¼ modified Glasgow Prognostic Score; MIC-1 ¼ macrophage inhibitory cytokine-1. (Selander et al, 2007;Brown et al, 2009), colorectal cancer , and glioblastoma (Shnaper et al, 2009). In this study, plasma MIC-1 also correlated significantly with mGPS and plasma CRP concentration, suggesting that MIC-1 might have a role in the aetiology of systemic inflammation in OGC (although linear regression implies that this may be a minor effect).…”

GDF15 derived from both tumor-associated macrophages and esophageal squamous cell carcinomas contributes to tumor progression via Akt and Erk pathways

“…19,30 In addition, serum GDF15 levels have been reported to be raised in patients with malignant glioma, pancreatic, or prostate carcinoma compared with those of healthy controls. 19,31,32 These previous findings may indicate that GDF15 exerts heterogeneous functions in tumors. However, the role of GDF15 in tumorigenesis is still unclear; for instance, a specific receptor for GDF15 has not been identified.…”

Growth/differentiation factor-15: prostate cancer suppressor or promoter?

“…84,85 Despite the presence of several molecular forms of GDF-15, the analysis of total GDF-15 serum levels showed its clear discriminative capacity for PCa mortality and disease outcome, which justifies further prospective studies to potentially introduce GDF-15 as a clinically important biomarker for PCa. 86 As such, the analysis of overall GDF-15 may offer a robust screening method.…”