Abstract
Growth differentiation factor 15 (GDF-15), a member of the transforming growth factor-β superfamily, participates in processes associated with myeloma development and its end-organ complications. It plays a significant role in both physiological and abnormal erythropoiesis and regulates iron homeostasis through modulation of hepcidin. It is abnormally secreted in marrow stromal cells of patients with multiple myeloma (MM), which may reflect the tumor microenvironment. We analyzed the associations of serum GDF-15 with clinical characteristics of 73 MM patients (including asymptomatic MM) and the laboratory indices of renal function, anemia, and inflammation. Baseline serum GDF-15 was studied as the predictor of two-year survival. We defined five clinically relevant subgroups of patients (symptomatic MM only, patients with and without remission, patients on chemotherapy, and without treatment). Increased GDF-15 concentrations were associated with more advanced MM stage, anemia, renal impairment (lower glomerular filtration and higher markers of tubular injury), and inflammation. Most of the results were confirmed in the subgroup analysis. Serum cystatin C and urine neutrophil gelatinase-associated lipocalin were associated with GDF-15 independently of other variables. In the studied MM patients, GDF-15 did not significantly predict survival (p = 0.06). Our results suggest that serum GDF-15 reflects myeloma burden and shares a relationship with several markers of prognostic significance, as well as major manifestations.
Highlights
Multiple myeloma (MM) is a common malignant condition resulting from a clonal proliferation of plasma cells in the bone marrow, which manifests itself with organ involvement, such as bone disease, anemia, and renal failure [1]
The prospective study recruited patients diagnosed with MM, assessed during their control ambulatory visits between August 2016 and October 2017
Our study examined an ambulatory care sample of patients with MM, demonstrating that serum Growth differentiation factor 15 (GDF-15) concentrations are significantly associated with myeloma characteristics, even in a diverse clinical population at various stages of disease
Summary
Multiple myeloma (MM) is a common malignant condition resulting from a clonal proliferation of plasma cells in the bone marrow, which manifests itself with organ involvement, such as bone disease, anemia, and renal failure [1]. The potential utility of GDF-15 in malignant neoplastic disease can be drawn from its unique characteristics of being a downstream target of tumor suppressor p53, with its only physiological presence at high levels in the placenta [6]. GDF-15 is considered a divergent member of the transforming growth factor β (TGFβ) family, which is induced in response to factors instigating cellular stress (e.g., hypoxia, tissue injury, and inflammation). These characteristics of GDF-15 suggest its increased concentration may be considered as an integrative, general marker for disease severity and mortality [6, 7]
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