title: Serum methionine metabolites are risk factors for metastatic prostate cancer progression.
abstract: BACKGROUND
  Clinical decision for primary treatment for prostate cancer is dictated by variables with insufficient specificity. Early detection of prostate cancer likely to develop rapid recurrence could support neo-adjuvant therapeutics and adjuvant options prior to frank biochemical recurrence. This study compared markers in serum and urine of patients with rapidly recurrent prostate cancer to recurrence-free patients after radical prostatectomy. Based on previous identification of urinary sarcosine as a metastatic marker, we tested whether methionine metabolites in urine and serum could serve as pre-surgical markers for aggressive disease.
  
  
  RESULTS
  Urine and serum samples (n = 54 and 58, respectively), collected at the time of prostatectomy were divided into subjects who developed biochemical recurrence within 2 years and those who remained recurrence-free after 5 years. Multiple methionine metabolites were measured in urine and serum by GC-MS. The role of serum metabolites and clinical variables (biopsy Gleason grade, clinical stage, serum prostate specific antigen [PSA]) on biochemical recurrence prediction were evaluated. Urinary sarcosine and cysteine levels were significantly higher (p = 0.03 and p = 0.007 respectively) in the recurrent group. However, in serum, concentrations of homocysteine (p = 0.003), cystathionine (p = 0.007) and cysteine (p<0.001) were more abundant in the recurrent population. The inclusion of serum cysteine to a model with PSA and biopsy Gleason grade improved prediction over the clinical variables alone (p<0.001).
  
  
  CONCLUSIONS
  Higher serum homocysteine, cystathionine, and cysteine concentrations independently predicted risk of early biochemical recurrence and aggressiveness of disease in a nested case control study. The methionine metabolites further supplemented known clinical variables to provide superior sensitivity and specificity in multivariable prediction models for rapid biochemical recurrence following prostatectomy.
authors.affiliation: Department of Medicine, University of Colorado, Aurora, Colorado, United States of America.
authors.forename: Sally
authors.initials: S
authors.lastname: Stabler
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Koyama
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Zhao
authors.forename: Magaly
authors.initials: M
authors.lastname: Martinez-Ferrer
authors.forename: Robert H
authors.initials: RH
authors.lastname: Allen
authors.forename: Zigmund
authors.initials: Z
authors.lastname: Luka
authors.forename: Lioudmila V
authors.initials: LV
authors.lastname: Loukachevitch
authors.forename: Peter E
authors.initials: PE
authors.lastname: Clark
authors.forename: Conrad
authors.initials: C
authors.lastname: Wagner
authors.forename: Neil A
authors.initials: NA
authors.lastname: Bhowmick
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood / Q000652:urine; D018450:Disease Progression; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008715:Methionine / Q000097:blood*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology* / Q000601:surgery / Q000652:urine; D012372:ROC Curve; D012008:Recurrence; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D008715:Methionine