title: Monocyte/macrophage-derived soluble CD163: a novel biomarker in multiple myeloma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Peripheral blood (n = 104) and bone marrow (n = 17) levels of sCD163 were measured using an enzyme-linked immunosorbent assay.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark; Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Morten N
authors.initials: MN
authors.lastname: Andersen
authors.forename: Niels
authors.initials: N
authors.lastname: Abildgaard
authors.forename: Maciej B
authors.initials: MB
authors.lastname: Maniecki
authors.forename: Holger J
authors.initials: HJ
authors.lastname: Møller
authors.forename: Niels F
authors.initials: NF
authors.lastname: Andersen
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000097:blood*; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000097:blood*; D016019:Survival Analysis; D016896:Treatment Outcome; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D014408:Biomarkers, Tumor; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface
keywords: CD163; biomarker; bone marrow microenvironment; macrophage; multiple myeloma