Use of thymosin beta15 as a urinary biomarker in human prostate cancer.
BACKGROUND
Additional prostate cancer (CaP) biomarkers are needed to increase the accuracy of diagnosis and to identify patients at risk of recurrence. In tissue-based assays, thymosin beta15 (Tbeta15) has been linked to an aggressive CaP phenotype and correlated with future tumor recurrence. We hypothesized that Tbeta15 may have clinical utility in biological fluids.


METHODS
Tbeta15 was measured in urine from CaP patients; untreated (N = 61), prostatectomy (RP, N = 46), androgen deprivation therapy (ADT, N = 14) and control groups; normal (N = 52), genitourinary carcinoma (N = 15), non-malignant prostate disease (N = 81), and other urology (N = 73). We evaluated the utility of urinary Tbeta15 for CaP diagnosis, alone or in combination with prostate-specific antigen (PSA), and the relationship to CaP progression.


RESULTS
A normal threshold of 40 (ng/dl)/(mug_protein/mg_creatinine) was defined using receiver operating characteristic analysis and marked the 19th centile for age-matched controls. The proportion of untreated CaP patients with urinary Tbeta15 above the threshold was significantly higher than normal and genitourinary disease controls (P < 0.001). RP caused urinary Tbeta15 to drop significantly (P = 0.005). Pre-surgery Tbeta15 concentrations greater than the normal threshold may confer greater risk of CaP recurrence. Relative to normal controls, patients receiving ADT for aggressive CaP were 12 times more likely to have elevated urinary Tbeta15 (P = 0.001, 95% CI = 2.8, 51.8). Combining PSA and Tbeta15 (PSA > 4, or PSA > 2.5, Tbeta15 > 40, or PSA = 2.5, Tbeta15 > 90) provided the same sensitivity as a 2.5 ng/ml PSA cutoff, but markedly improved diagnostic specificity.


CONCLUSIONS
We report that Tbeta15 is a urinary biomarker for CaP and suggest that Tbeta15, in combination with PSA, can be used to improve both the sensitivity and specificity of CaP diagnosis.
Hutchinson
Lloyd M
LM
Program in Vascular Biology and Department of Surgery, Children's Hospital, Boston, MA 02115, USA.
Chang
Eric L
EL
Becker
Christian M
CM
Shih
Mei-Chiung
MC
Brice
Mark
M
DeWolf
William C
WC
Gaston
Sandra M
SM
Zetter
Bruce R
BR
D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000652:urine*; D018450:Disease Progression; D006801:Humans; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011237:Predictive Value of Tests; D017430:Prostate-Specific Antigen / Q000652:urine; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000628:therapy / Q000652:urine*; D013947:Thymosin / Q000652:urine*
D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; C525161:thymosin beta15, rat; D013947:Thymosin; D017430:Prostate-Specific Antigen