International journal of cancer. Journal international du cancer
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The circulating levels of several angiogenic cytokines [angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), angiogenin and basic fibroblast growth factor (bFGF)] were evaluated in 174 consecutive patients with newly diagnosed, symptomatic, multiple myeloma (MM). Circulating levels of Ang-1/Ang-2 were reduced in myeloma patients compared to controls, whereas VEGF and angiogenin levels were increased. Reduced angiopoietin-1/angiopoietin-2 ratio correlated with advanced disease features including international staging system (ISS)-3 stage, renal impairment and extensive bone disease. ⋯ Furthermore, a subset of ISS-3 patients with serum Ang-1/Ang-2 above the median value had favourable prognosis (median survival: 45 months versus 17 months of all others; p = 0.0001). The multivariate analysis revealed that low Ang-1/Ang-2 ratio could independently predict for inferior survival in our cohort of patients (relative risk (RR) 2.07, 95% CI 1.50-2.42; p < 0.001). These results highlight the role of angiopoietins pathway in the biology of MM and reveal novel targets for the development of antimyeloma agents.