Haraguchi Kouichi, Uto Hirofumi, Ohnou Nobuhito, Tokunaga Masahito, Tokunaga Mayumi, Utsunomiya Atae, Hanada Shuichi, Tsubouchi Hirohito
Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544; ; Department of Hematology, National Hospital Organization Kagoshima Medical Center, Kagoshima 892-0853;
Exp Ther Med. 2012 Oct;4(4):581-588. doi: 10.3892/etm.2012.663. Epub 2012 Aug 18.
Prohepcidin is the prohormone of hepcidin. Anemia is one of the main clinical features in patients with multiple myeloma (MM) and hepcidin may be associated with iron homeostasis in these patients. However, the clinical significance of prohepcidin is not fully understood. In this retrospective study, we measured serum prohepcidin levels using an immunoassay technique to study its clinical significance in 39 MM patients. Serum prohepcidin levels in patients with MM were weakly correlated with alkaline phosphatase (ALP) levels (r=0.32, P=0.048), calculated by Spearman's rank correlation, but not with other clinical data, including hemoglobin, serum iron or ferritin. In addition, patients with severe renal insufficiency [creatinine clearance (CCr) <50 ml/min] had significantly higher prohepcidin levels compared with patients with mild or no renal insufficiency (CCr ≥50 ml/min, P=0.047). In contrast, low serum prohepcidin levels less than 110 ng/ml were an independent predictor of poor overall survival [hazard ratio (HR), 5.29; 95% confidence interval (CI), 1.65-17.03] in addition to serum creatinine levels of at least 2 mg/dl (HR, 5.32; CI, 1.10-25.64), serum calcium (HR, 3.53; CI, 1.01-12.33) and ECOG performance status grade 4 (HR, 4.15; CI, 1.32-13.09) in the multivariate analysis using Cox proportional hazards model. In the subset of 31 MM patients with CCr ≥50 ml/min, low serum prohepcidin (HR, 5.65; CI, 1.60-19.95) was an indicator of poor prognosis in multivariate analysis. These results indicate that serum prohepcidin levels may be associated with ALP and renal function but not iron homeostasis, in MM patients. In addition, lower serum prohepcidin levels are potential independent indicators of poor overall survival in MM patients regardless of renal function.
前铁调素是铁调素的前体激素。贫血是多发性骨髓瘤（MM）患者的主要临床特征之一，前铁调素可能与这些患者的铁稳态有关。然而，前铁调素的临床意义尚未完全明确。在这项回顾性研究中，我们使用免疫分析技术测量了39例MM患者的血清前铁调素水平，以研究其临床意义。MM患者的血清前铁调素水平与碱性磷酸酶（ALP）水平呈弱相关（r = 0.32，P = 0.048），采用Spearman等级相关计算，但与其他临床数据无关，包括血红蛋白、血清铁或铁蛋白。此外，与轻度或无肾功能不全（肌酐清除率[CCr]≥50 ml/min）的患者相比，严重肾功能不全（CCr<50 ml/min）的患者前铁调素水平显著更高（P = 0.047）。相反，在使用Cox比例风险模型的多变量分析中，血清前铁调素水平低于110 ng/ml是总体生存不良的独立预测因素[风险比（HR），5.29；95%置信区间（CI），1.65 - 17.03]，此外还有血清肌酐水平至少为2 mg/dl（HR，5.32；CI，1.10 - 25.64）、血清钙（HR，3.53；CI，1.01 - 12.33）和东部肿瘤协作组（ECOG）体能状态4级（HR，4.15；CI，1.32 - 13.09）。在31例CCr≥50 ml/min的MM患者亚组中，低血清前铁调素（HR，5.65；CI，1.60 - 19.95）在多变量分析中是预后不良的指标。这些结果表明，MM患者的血清前铁调素水平可能与ALP和肾功能有关，但与铁稳态无关。此外，无论肾功能如何，较低的血清前铁调素水平都是MM患者总体生存不良的潜在独立指标。
