title: Composite three-marker assay for early detection of kidney cancer.
abstract: BACKGROUND
  Early detection of renal cell carcinoma using serum/plasma biomarkers remains challenging. To validate clinical performance of potential candidate markers for kidney tumors, three-marker assay composed of nicotinamide N-methyltransferase (NNMT), L-plastin (LCP1), and nonmetastatic cells 1 protein (NM23A) was evaluated.
  
  
  METHODS
  Patients with kidney cancer and control group were included in the clinical evaluation. Participants were divided into cohorts representing the training group of control group including healthy and benign tumors (n = 102) and patients with kidney cancer (n = 87) that were used to identify criteria for scoring. Then, we developed a three-marker assay that was validated with a cohort of test group samples (n = 100). A scoring method based on the cut-point of each of the three markers was used to evaluate the diagnostic performance of the marker combination.
  
  
  RESULTS
  Plasma levels of NNMT, LCP1, and NM23A were highly elevated in patients with kidney cancer (P < 0.0001). In 289 blind sample tests with control subjects (n = 175) and patients with kidney cancer (n = 114), the diagnostic accuracy of NNMT alone and the three-marker assay was 0.913 and 0.932, respectively. When 90% specificity was defined, the sensitivity of NNMT and the three-marker assay was 71.9% and 95.7%, respectively. The predictive value of the three-marker assay was 87.2% (+PPV) and 97% (-PPV).
  
  
  CONCLUSIONS
  The composite assay with NNMT, LCP1, and NM23A was a promising novel serum marker assay for the early detection of malignant kidney tumors covering subtypes of RCC with high diagnostic characteristics.
  
  
  CONCLUSIONS
  NNMT/LCP1/NM23A triple markers could be a helpful screening assay to detect early RCC.
authors.affiliation: Corresponding Author: Nam Hoon Cho, Department of Pathology, Yonsei University College of Medicine & The Severance Biomedical Science Institute, Seoul, Korea.
authors.forename: Dong
authors.initials: D
authors.lastname: Su Kim
authors.forename: Young Deuk
authors.initials: YD
authors.lastname: Choi
authors.forename: Mihyang
authors.initials: M
authors.lastname: Moon
authors.forename: Suki
authors.initials: S
authors.lastname: Kang
authors.forename: Jong-Baeck
authors.initials: JB
authors.lastname: Lim
authors.forename: Kyung Min
authors.initials: KM
authors.lastname: Kim
authors.forename: Kyung Mok
authors.initials: KM
authors.lastname: Park
authors.forename: Nam Hoon
authors.initials: NH
authors.lastname: Cho
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood*; D002291:Carcinoma, Papillary / Q000097:blood / Q000175:diagnosis; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000175:diagnosis; D002295:Carcinoma, Transitional Cell / Q000097:blood / Q000175:diagnosis; D016022:Case-Control Studies; D042241:Early Diagnosis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007680:Kidney Neoplasms / Q000097:blood / Q000175:diagnosis*; D008297:Male; D008840:Microfilament Proteins / Q000097:blood*; D008875:Middle Aged; D054778:NM23 Nucleoside Diphosphate Kinases / Q000097:blood*; D009367:Neoplasm Staging; D050903:Nicotinamide N-Methyltransferase / Q000097:blood*; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; C047262:LCP1 protein, human; D008840:Microfilament Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; C494406:NNMT protein, human; D050903:Nicotinamide N-Methyltransferase