Contribution to the Evaluation of the Relationship between Angiogenic Cytokines, Selected Biological Parameters and Prognostic Factors in Multiple Myeloma

Overview

Background.
Multiple myeloma is an unusually heterogeneous disease with individually different clinical course, sensitivity to therapy and prognosis. The undoubted limitation of contemporary diagnostic stratification systems is the insufficient credit of those parameters that express the intrinsic biological properties of myeloma cells and the microenvironment of the bone marrow. The aim of this study was to evaluate the relationship of 10 biological parameters to 6 fundamental prognostic factors of multiple myeloma. 

Methods and Results.
The analysed group consisted of 66 individuals examined at the time of diagnosis before the start of therapy. For the estimation of serum levels of investigated molecules there were used following methods: REA RIA, ELISA and the technique of quantitative sandwich enzyme immunoassay. For the analysis of proliferative and apoptotic properties of myeloma cells we used propidium iodide (PC-PI) and annexin-V (PC-AI) indices. The statistical estimation was carried out with the help of Pearson and Spearman test, eventually with the help of U-test according to Mann–Whitney. Increased incidence of abnormal serum levels of examined parameter was registered in the case of S-β₂-microglobulin (95.5 %), S-thymidinekinase (57.5 %), S-sVCAM-1 (78.5 %), S-ICTP (87.0 %), S-solubile osteoprotegerin (sOPG 76.5 %), S-sSyndecan-1 (56.5 %) and low index of plasma cell apoptosis (PC-AI, 78.0 %). The statistical analysis (Pearson’s test) revealed the mutual relationship of serum levels of: S-β₂-microglobulin to sVCAM-1, (r=0.39, p=0.002), sICAM-1 (r=0.33, p=0.011), sOPG (r=0.53, p=0.001), sHGF (r=0.34, p= 0.006), sSyndecan-1 (r=0.38, p=0.003) and sFas (r=0.42, p=0.001); S-albumin to sVCAM-1 (r= -0.29, p=0.036), ICTP (r= -0.33, p=0.016), sOPG (r= -0.63, p=0.000), sHGF (r= -0.39, p=0.003), sSyndecan-1 (r= -0.29, p=0.042); S-thymidinekinase to sSyndecan-1 (r=0.46, p=0.000) and sFas (r=0.29, p=0.019). There was no zjišrelationship of PINP and VEGF to any of the evaluated prognostic factors. There was no relationship found between either of the analysed parameters to PC-PI and PC-AI. With the help of U-test there was found the relationship of sIL-6R to S-β₂-microglobulin (p=0.001), albumin (p=0.002) and PC-PI (p=0.046). 

Conclusions.
The presented study implies that the traditional algorithm of parameters used in clinical practice for individual characteristics of MM should be enriched with sOPG, sHGF, sSyndecan-1 and sFas. 

Key words:
multiple myeloma, S-β₂-microglobulin, proliferation index, soluble receptor IL-6, vascular cytoadhesive molecule-1, C-terminal telopeptide collagen I, hepatocyte growth factor, osteoprotegerin, syndecan-1, Fas.