title: CD163+CD14+ macrophages, a potential immune biomarker for malignant pleural effusion.
abstract: BACKGROUND
  Malignant pleural effusion (MPE) is a common complication caused by malignant diseases. However, subjectivity, poor sensitivity, and substantial false-negative rates of cytology assay hamper accurate MPE diagnosis. The aim of this study was to assess whether CD163+CD14+ tumor-associated macrophages (TAMs) could be used as a biomarker for enabling sensitive and specific MPE diagnosis.
  
  
  METHODS
  Pleural effusion samples and peripheral blood samples were collected from 50 MPE patients and 50 non-malignant pleural effusion (NMPE) patients, respectively. Flow cytometry was performed to analyze cell phenotypes, and RT-qPCR was used to detect cytokine expression in these monocytes and macrophages. A blinded validation study (n = 40) was subsequently performed to confirm the significance of CD163+CD14+ TAMs in MPE diagnosis. Student's t test, rank sum test, and receiver operating characteristic curve analysis were used for statistical analysis.
  
  
  RESULTS
  Notably, CD163+CD14+ cell frequency in MPE was remarkably higher than that in NMPE (P < 0.001). In a blinded validation study, a sensitivity of 78.9 % and a specificity of 100 % were obtained with CD163+CD14+ TAMs as a MPE biomarker. In total (n = 140), by using a cutoff level of 3.65 %, CD163+CD14+ cells had a sensitivity of 81.2 % and a specificity of 100 % for MPE diagnosis. Notably, MPE diagnosis by estimating CD163+CD14+ cells in pleural effusion could be obtained one week earlier than that obtained by cytological examination.
  
  
  CONCLUSIONS
  CD163+CD14+ macrophages could be potentially used as an immune diagnostic marker for MPE and has better assay sensitivity than that of cytological analysis.
authors.affiliation: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, Henan Province, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Qun
authors.initials: Q
authors.lastname: Gao
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Shengdian
authors.initials: S
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D015703:Antigens, CD / Q000032:analysis* / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis* / Q000276:immunology; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000276:immunology; D002469:Cell Separation; D016207:Cytokines / Q000378:metabolism; D003937:Diagnosis, Differential; D005189:False Positive Reactions; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D018950:Lipopolysaccharide Receptors / Q000032:analysis* / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D016066:Pleural Effusion, Malignant / Q000175:diagnosis* / Q000276:immunology; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000276:immunology; D012680:Sensitivity and Specificity; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D014408:Biomarkers, Tumor; D000098902:CD163 Antigen; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D011956:Receptors, Cell Surface