Serum methionine metabolites are risk factors for metastatic prostate cancer progression

• Published in: PloS one Vol. 6; no. 8; p. e22486
• Main Authors: Stabler, Sally, Koyama, Tatsuki, Zhao, Zhiguo, Martinez-Ferrer, Magaly, Allen, Robert H, Luka, Zigmund, Loukachevitch, Lioudmila V, Clark, Peter E, Wagner, Conrad, Bhowmick, Neil A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.08.2011; Public Library of Science (PLoS)
• Subjects: Amino acids; Biochemistry; Biology; Biomarkers, Tumor - blood; Biomarkers, Tumor - urine; Biopsy; Cancer; Cancer diagnosis; Cancer metastasis; Cancer research; Cancer surgery; Cancer treatment; Cysteine; Development and progression; Disease control; Disease Progression; Health risk assessment; Health risks; Homocysteine; Humans; Kaplan-Meier Estimate; Logistic Models; Male; Markers; Mathematical models; Medicine; Metabolites; Metastases; Methionine; Methionine - blood; Middle Aged; Neoplasm Metastasis; Patients; Prediction models; Proportional Hazards Models; Prostate cancer; Prostate specific antigen; Prostatectomy; Prostatic Neoplasms - blood; Prostatic Neoplasms - pathology; Prostatic Neoplasms - surgery; Prostatic Neoplasms - urine; Recurrence; Recurrence (Disease); Risk analysis; Risk Factors; ROC Curve; Rodents; Sarcosine; Surgery; Urine; Urological surgery; Puerto Rico; United States > US; Colorado; Tennessee; Nashville Tennessee
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0022486

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. 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). 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.