Terzi Demirsoy Esra, Mehtap Ozgür, Birtas Atesoglu Elif, Tarkun Pinar, Gedük Ayfer, Eren Necmi, Hacihanefioglu Abdullah
Department of Hematology, Derince Training and Research Hospital, Health Sciences University, 41900 Derince, Kocaeli Turkey.
Department of Hematology, Kocaeli University School of Medicine, Kocaeli, Turkey.
Indian J Hematol Blood Transfus. 2022 Jul;38(3):454-463. doi: 10.1007/s12288-021-01470-5. Epub 2021 Jul 13.
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 ( = 0.008). Additionally, low sKL levels were related to decreased overall survival, but they didn't reach statistically significant ( = 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.
多发性骨髓瘤是一种常见累及骨骼的浆细胞恶性肿瘤。成纤维细胞生长因子-23（FGF-23）/α-klotho通路在矿物质代谢中起主要作用，其中FGF-23具有抑制矿化作用。α-klotho还通过作为肿瘤抑制基因发挥抗凋亡和抗肿瘤作用。血清FGF-23与血清可溶性α-klotho（sKL）水平呈负相关。因此，研究sKL和FGF-23作为多发性骨髓瘤患者的生物标志物具有重要意义。我们采用酶联免疫吸附测定法检测了55例新诊断的多发性骨髓瘤患者和23例健康对照者的血清FGF-23和sKL水平。与健康对照相比，我们发现多发性骨髓瘤患者的血清FGF-23显著升高，血清sKL水平降低。血清sKL水平与p53阳性突变状态、高国际分期系统（ISS）、乳酸脱氢酶升高、C反应蛋白、β2微球蛋白水平呈负相关。血清FGF-23水平与血清磷呈负相关，仅与轻链和p53突变呈正相关。血清FGF-23水平高的患者中位总生存期明显短于血清FGF-23水平低的患者（P = 0.008）。此外，低sKL水平与总生存期降低有关，但未达到统计学显著性（P = 0.072）。多发性骨髓瘤患者血清sKL降低、FGF-23水平升高与已知预后因素之间存在显著相关性。我们得出结论，低sKL和高FGF-23水平可能是多发性骨髓瘤患者预后不良的生物标志物。
