title: Preliminary evaluation of urinary soluble Met as a biomarker for urothelial carcinoma of the bladder.
abstract: BACKGROUND
  Among genitourinary malignancies, bladder cancer (BCa) ranks second in both prevalence and cause of death. Biomarkers of BCa for diagnosis, prognosis and disease surveillance could potentially help prevent progression, improve survival rates and reduce health care costs. Among several oncogenic signaling pathways implicated in BCa progression is that of hepatocyte growth factor (HGF) and its cell surface receptor, Met, now targeted by 25 experimental anti-cancer agents in human clinical trials. The involvement of this pathway in several cancers is likely to preclude the use of urinary soluble Met (sMet), which has been correlated with malignancy, for initial BCa screening. However, its potential utility as an aid to disease surveillance and to identify patients likely to benefit from HGF/Met-targeted therapies provide the rationale for this preliminary retrospective study comparing sMet levels between benign conditions and primary BCa, and in BCa cases, between different disease stages.
  
  
  METHODS
  Normally voided urine samples were collected from patients with BCa (Total: 183; pTa: 55, pTis: 62, pT1: 24, pT2: 42) and without BCa (Total: 83) on tissue-procurement protocols at three institutions and sMet was measured and normalized to urinary creatinine. Normalized sMet values grouped by pathologic stage were compared using non-parametric tests for correlation and significant difference. ROC analyses were used to derive classification models for patients with or without BCa and patients with or without muscle-invasive BCa (MIBCa or NMIBCa).
  
  
  RESULTS
  Urinary sMet levels accurately distinguished patients with BCa from those without (p<0.0001, area under the curve (AUC): 0.7008) with limited sensitivity (61%) and moderate specificity (76%), and patients with MIBCa (n=42) from those with NMIBCa (n=141; p<0.0001, AUC: 0.8002) with moderate sensitivity and specificity (76% and 77%, respectively) and low false negative rate (8%).
  
  
  CONCLUSIONS
  Urinary sMet levels distinguish patients with BCa from those without, and patients with or without MIBCa, suggesting the potential utility of urinary sMet as a BCa biomarker for surveillance following initial treatment. Further studies are warranted to determine its potential value for prognosis in advanced disease, predicting treatment response, or identifying patients likely to benefit from Met-targeted therapies.
authors.forename: Brian K
authors.initials: BK
authors.lastname: McNeil
authors.forename: Maximiliano
authors.initials: M
authors.lastname: Sorbellini
authors.forename: Robert L
authors.initials: RL
authors.lastname: Grubb
authors.forename: Andrea
authors.initials: A
authors.lastname: Apolo
authors.forename: Fabiola
authors.initials: F
authors.lastname: Cecchi
authors.forename: Gagani
authors.initials: G
authors.lastname: Athauda
authors.forename: Benjamin
authors.initials: B
authors.lastname: Cohen
authors.forename: Alessio
authors.initials: A
authors.lastname: Giubellino
authors.forename: Haley
authors.initials: H
authors.lastname: Simpson
authors.forename: Piyush K
authors.initials: PK
authors.lastname: Agarwal
authors.forename: Jonathan
authors.initials: J
authors.lastname: Coleman
authors.forename: Robert H
authors.initials: RH
authors.lastname: Getzenberg
authors.forename: George J
authors.initials: GJ
authors.lastname: Netto
authors.forename: Joanna
authors.initials: J
authors.lastname: Shih
authors.forename: W Marston
authors.initials: WM
authors.lastname: Linehan
authors.forename: Peter A
authors.initials: PA
authors.lastname: Pinto
authors.affiliation: Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bldg 10, Hatfield Clinical Research Center, Rm 2 W-3952 10 Center Drive MSC 1210, 20892-1210, Bethesda, MD, USA. don.bottaro@nih.gov.
authors.forename: Donald P
authors.initials: DP
authors.lastname: Bottaro
mesh_terms: D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000652:urine*; D016022:Case-Control Studies; D006801:Humans; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D019859:Proto-Oncogene Proteins c-met / Q000652:urine*; D012372:ROC Curve; D012680:Sensitivity and Specificity; D012995:Solubility; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000652:urine*; D019459:Urothelium / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D019859:Proto-Oncogene Proteins c-met