title: The combination assay with circulating vascular endothelial growth factor (VEGF)-C, matrix metalloproteinase-9, and VEGF for diagnosing lymph node metastasis in patients with non-small cell lung cancer.
abstract: BACKGROUND
  The aim of the present study was to evaluate the diagnostic utility of levels of circulating vascular endothelial growth factor (VEGF)-C, matrix metalloproteinase-9 (MMP-9), and VEGF and to verify that the combination assay of these circulating factors is a clinically useful indicator to predict the presence of lymph node metastasis in non-small cell lung cancer (NSCLC).
  
  
  METHODS
  A series of 78 patients who underwent surgery for NSCLC was used in this study. Serum VEGF-C and VEGF and plasma MMP-9 levels were analyzed with enzyme-linked immunosorbent assay (ELISA) kits. Logistic regression models were used to analyze the influence of VEGF-C, MMP, and VEGF levels on the probability of presence or absence of lymph node metastasis.
  
  
  RESULTS
  Patients with lymph node metastasis had higher serum VEGF- C, VEGF, and plasma MMP-9 concentrations than did those without metastasis (VEGF-C, P = .0004; VEGF, P = .001). Serum VEGF- C reached a sensitivity of 85% and specificity of 68% when a cutoff value of 1762.0 pg/mL was applied, while VEGF reached 80% sensitivity and 59% specificity at 316.8 pg/mL. MMP-9 reached a sensitivity of 63% and specificity of 75% when a cutoff value of 51.4 ng/mL was applied. In the ROC curve analysis, VEGF-C (0.761) had the biggest areas under the ROC curve, followed by MMP-9 (0.723) and VEGF (0.694). Combination assay of three markers had higher sensitivity and specificity for prediction than single-marker assays (AUC = 0.837).
  
  
  CONCLUSIONS
  This study has confirmed that combination assay of three markers to determine VEGF-C, MMP-9, and VEGF expression in circulation detects lymph node metastasis in NSCLC with higher accuracy than single-marker assays.
authors.affiliation: Department of General and Cardiothoracic Surgery, Kanazawa University School of Medicine, Takara-machi 13-1, Ishikawa, Kanazawa 920-8641, Japan. m-tamura@sf.m.kanazawa-u.ac.jp
authors.forename: Masaya
authors.initials: M
authors.lastname: Tamura
authors.forename: Makoto
authors.initials: M
authors.lastname: Oda
authors.forename: Isao
authors.initials: I
authors.lastname: Matsumoto
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Tsunezuka
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Kawakami
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Ohta
authors.forename: Go
authors.initials: G
authors.lastname: Watanabe
mesh_terms: D000328:Adult; D000368:Aged; D001681:Biological Assay / Q000379:methods; D014408:Biomarkers, Tumor / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology* / Q000601:surgery; D008207:Lymphatic Metastasis / Q000175:diagnosis*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D012680:Sensitivity and Specificity; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D042582:Vascular Endothelial Growth Factor C / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D020780:Matrix Metalloproteinase 9