Prognostic Value of Serum Soluble Klotho and Fibroblast Growth Factor-23 in Multiple Myeloma Patients

Abstract

Multiple myeloma is the plasma cell malignancy in which bone involvement is common. The Fibroblast growth factor-23 (FGF-23)/Klotho pathway plays a major role in mineral metabolism that FGF-23 is mineralization inhibitory. Klotho also has anti-apoptotic and anti-tumor effects by acting as a tumor suppressor gene. There is a negative correlation between serum FGF-23 and serum soluble Klotho (sKL) levels. As such, there can be considerable interest in investigating sKL and FGF-23 as a biomarker in patients with MM. We used an enzyme-linked immunosorbent assay to measure serum FGF-23 and sKL levels in 55 newly diagnosed MM patients and 23 healthy controls. We determined significantly high serum FGF-23 and low serum sKL levels in MM patients when compared to healthy controls. Serum sKL levels correlated negatively with a p53 positive mutation status, with high ISS, elevated lactate dehydrogenase, C-reactive protein, Beta-2 microglobulin levels. Serum FGF-23 levels are associated negatively with serum phosphorus and positively only light chains and p53 mutation. Patients with high serum FGF-23 levels had significantly shorter median overall survival than those with low serum FGF-23 levels (p = 0.008). Additionally, low sKL levels were related to decreased overall survival, but they didn't reach statistically significant (p = 0.072). There is a significant correlation between low serum sKL, high FGF-23 levels, and known prognostic factors in MM patients. We conclude that low sKL and high FGF-23 levels are a probable prognostic biomarker for poor MM patient outcomes.

Keywords: Fibroblast growth factor (FGF)-23; Klotho; Multiple myeloma; Survival outcomes.

Fig. 1

a Serum sKL level in MM patients and healthy controls. The median serum sKL concentration in MM patients was (402.46 pg/mL; range 115.38–667.35) that was significantly lower than serum sKLconcentration (565.21 pg/mL; range 384.1–770.41) in the healthy controls (p ≤ 0.001). b Serum FGF-23 level in MM patients and healthy controls. The serum FGF-23 level of MM patients was (131.67 pg/mL; range 31.25–2000) significantly higher than HC (31.25 pg/mL; range 28.02–2000) (p ≤ 0.001)

Fig. 2

a OS analysis in MM patients. Serum low sKL level < 402.46 pg/mL was associated with shorter OS. But, it was not statistically significant (p = 0.072). b OS analysis in MM patients. Serum high sFGF-23 level > 131.67 pg/mL was associated with shorter OS (p = 0.008)