Serum galectin-1 in patients with multiple myeloma: associations with survival, angiogenesis, and biomarkers of macrophage activation

Abstract

Galectin-1 (Gal-1) is known to regulate cell signaling within the immune system and may be a target for new anticancer immune therapy. In patients with chronic lymphocytic leukemia (CLL) and classical Hodgkin lymphoma (cHL), high levels of Gal-1 within the tumor microenvironment were associated with worse disease state or poor outcome. Gal-1 can be secreted from cells by an unknown mechanism, and levels in blood samples were associated with high tumor burden and worse disease state in cHL and CLL patients. However, serum levels of Gal-1 have never been investigated in patients with multiple myeloma (MM). We measured serum Gal-1 levels in samples from patients with treatment demanding MM at the time of diagnosis (n=102) and after treatment (n=24) and examined associations of serum Gal-1 with clinicopathological information obtained from patient medical records, as well as data on bone marrow angiogenesis and the macrophage activation biomarkers soluble CD163 (sCD163) and soluble mannose receptor. Serum Gal-1 levels were not elevated in patients with MM at diagnosis compared with healthy donors (median values 8.48 vs 11.93 ng/mL, P=0.05), which is in contrast to results in cHL and CLL. Furthermore, Gal-1 levels did not show association with bone marrow angiogenesis, clinicopathological parameters, overall survival, or response to treatment. There was a statically significant association between Gal-1 and sCD163 levels (R=0.24, P=0.02), but not with soluble mannose receptor (P=0.92). In conclusion, our results indicate that Gal-1 is not an important serum biomarker in MM, which is in contrast to data from patients with cHL and CLL. However, the association with sCD163 is in line with previous data showing that Gal-1 may be involved in alternative (M2-like) activation of macrophages.

Keywords: angiogenesis; galectin-1; macrophage; multiple myeloma; soluble CD163; soluble mannose receptor.

Figure 1

Serum Gal-1 in MM patients pre- and posttreatment. Notes: Serum Gal-1 levels in healthy donors (n=30), patients with newly diagnosed MM (n=102), and for MM patients 3 months after HDT (n=24). Bars show median and interquartile range. *P=0.05. Abbreviations: Gal-1, galectin-1; HDT, high dose treatment; MM, multiple myeloma; NS, not significant.

Figure 2

Serum Gal-1 in multiple myeloma patients according to ISS stage. Notes: Serum Gal-1 levels at time of diagnosis in patients with multiple myeloma, stratified by ISS stage. Bars show median and interquartile range. Abbreviations: Gal-1, galectin-1; ISS, international staging system; NS, not significant.

Figure 3

Serum Gal-1 and bone marrow angiogenesis. Notes: Serum Gal-1 levels at time of diagnosis, stratified by bone marrow angiogenesis level measured as MVD, spilt on median MVD. Bars show median and interquartile range. Abbreviations: Gal-1, galectin-1; MVD, micro-vessel density; NS, not significant.

Figure 4

Associations of serum Gal-1 with macrophage and plasma cell markers. Notes: Serum Gal-1 levels at time of diagnosis in patients with multiple myeloma were positively associated with levels of (A) serum syndecan-1 (sCD138, R=0.36, P=0.01) and (B) serum sCD163 (R=0.24, P=0.02). Plotted parameters were log-transformed using the natural logarithmic function. Abbreviations: Gal-1, galectin-1; sCD138, soluble CD138.