Andersen Morten N, Abildgaard Niels, Maniecki Maciej B, Møller Holger J, Andersen Niels F
Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark; Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Eur J Haematol. 2014 Jul;93(1):41-7. doi: 10.1111/ejh.12296. Epub 2014 Mar 20.
Macrophages play an important role in cancer by suppression of adaptive immunity and promotion of angiogenesis and metastasis. Tumor-associated macrophages strongly express the hemoglobin scavenger receptor CD163, which can also be found as a soluble protein in serum and other body fluids (soluble CD163, sCD163). In this study, we examined serum sCD163 as a biomarker in patients with newly diagnosed multiple myeloma.
Peripheral blood (n = 104) and bone marrow (n = 17) levels of sCD163 were measured using an enzyme-linked immunosorbent assay.
At diagnosis, high sCD163 was associated with higher stage according to the International Staging System (ISS) and with other known prognostic factors in multiple myeloma (creatinine, C-reactive protein, and beta-2 microglobulin). Soluble CD163 decreased upon high-dose treatment, and in a multivariate survival analysis including the covariates treatment modality and age at diagnosis, higher levels of sCD163 were associated with poor outcome (HR = 1.82; P = 0.010). The prognostic significance of sCD163 was lost when including ISS stage in the model (HR = 1.51; P = 0.085). Soluble CD163 values were significantly higher in bone marrow samples than in the matched blood samples, which indicate a localized production of sCD163 within the bone marrow microenvironment.
Soluble CD163 was found to be a prognostic marker in patients with multiple myeloma. This may indicate that macrophages and/or monocytes have an important role in the bone marrow microenvironment of myeloma patients, supporting myeloma cell proliferation and survival. We propose the serum sCD163 value 1.8 mg/L as a cutoff concentration for survival analysis in patients with multiple myeloma, which should be validated in future studies.
巨噬细胞通过抑制适应性免疫以及促进血管生成和转移，在癌症中发挥重要作用。肿瘤相关巨噬细胞强烈表达血红蛋白清除受体CD163，其在血清和其他体液中也以可溶性蛋白形式存在（可溶性CD163，sCD163）。在本研究中，我们检测了血清sCD163作为新诊断多发性骨髓瘤患者生物标志物的情况。
采用酶联免疫吸附测定法测量外周血（n = 104）和骨髓（n = 17）中sCD163的水平。
诊断时，根据国际分期系统（ISS），高sCD163与更高分期相关，并且与多发性骨髓瘤的其他已知预后因素（肌酐、C反应蛋白和β2微球蛋白）相关。高剂量治疗后可溶性CD163降低，在一项包括协变量治疗方式和诊断时年龄的多因素生存分析中，较高水平的sCD163与不良预后相关（风险比=1.82；P = 0.010）。当模型中纳入ISS分期时，sCD163的预后意义消失（风险比=1.51；P = 0.085）。骨髓样本中的可溶性CD163值显著高于匹配的血液样本，这表明sCD163在骨髓微环境中呈局部产生。
可溶性CD163被发现是多发性骨髓瘤患者的一个预后标志物。这可能表明巨噬细胞和/或单核细胞在骨髓瘤患者的骨髓微环境中起重要作用，支持骨髓瘤细胞的增殖和存活。我们建议将血清sCD163值1.8mg/L作为多发性骨髓瘤患者生存分析的临界浓度，这应在未来研究中得到验证。
