title: Plasma markers for identifying patients with metastatic melanoma.
abstract: OBJECTIVE
  With the rising incidence of melanoma, more patients are undergoing surveillance for disease recurrence. Our purpose was to study levels of proteins that might be secreted in the blood of patients with metastatic melanoma that can be used for monitoring these individuals.
  
  
  METHODS
  Genome-wide gene expression data were used to identify abundantly expressed genes in melanoma cells that encode for proteins likely to be present in the blood of cancer patients, based on high expression levels in tumors. ELISA assays were employed to measure proteins in plasma of 216 individuals; 108 metastatic melanoma patients and 108 age- and gender-matched patients with resected stage I/II disease split into equal-sized training and test cohorts.
  
  
  RESULTS
  Levels of seven markers, CEACAM (carcinoembryonic antigen-related cell adhesion molecule), ICAM-1 (intercellular adhesion molecule 1), osteopontin, MIA (melanoma inhibitory activity), GDF-15 (growth differentiation factor 15), TIMP-1 (tissue inhibitor of metalloproteinase 1), and S100B, were higher in patients with unresected stage IV disease than in patients with resected stage I/II disease. About 81% of the stage I/II patients in the training set had no marker elevation, whereas 69% of the stage IV patients had elevation of at least one marker (P < 0.0001). Receiver operating characteristic curves for the markers in combination in these two patient populations had an area under curve (AUC) of 0.79 in the training set and 0.8 in the test set. A CART (Classification and Regression Trees) model developed in the training set further improved the AUC in the test set to 0.898.
  
  
  CONCLUSIONS
  Plasma markers, particularly when assessed in combination, can be used to monitor patients for disease recurrence and can compliment currently used lactate dehydrogenase and imaging studies; prospective validation is warranted.
authors.affiliation: Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: Harriet M
authors.initials: HM
authors.lastname: Kluger
authors.forename: Kathleen
authors.initials: K
authors.lastname: Hoyt
authors.forename: Antonella
authors.initials: A
authors.lastname: Bacchiocchi
authors.forename: Tina
authors.initials: T
authors.lastname: Mayer
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kirsch
authors.forename: Yuval
authors.initials: Y
authors.lastname: Kluger
authors.forename: Mario
authors.initials: M
authors.lastname: Sznol
authors.forename: Stephan
authors.initials: S
authors.lastname: Ariyan
authors.forename: Annette
authors.initials: A
authors.lastname: Molinaro
authors.forename: Ruth
authors.initials: R
authors.lastname: Halaban
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D015815:Cell Adhesion Molecules / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D016326:Extracellular Matrix Proteins / Q000097:blood; D005260:Female; D006023:Glycoproteins / Q000097:blood; D055436:Growth Differentiation Factor 15 / Q000097:blood; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000473:pathology / Q000601:surgery; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000097:blood; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000175:diagnosis; D009367:Neoplasm Staging; D009414:Nerve Growth Factors / Q000097:blood; D011379:Prognosis; D015203:Reproducibility of Results; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood; D012680:Sensitivity and Specificity; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D055436:Growth Differentiation Factor 15; C090059:MIA protein, human; D009363:Neoplasm Proteins; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C024229:osteopoietin; D018799:Intercellular Adhesion Molecule-1; D007770:L-Lactate Dehydrogenase