Use of thymosin β15 as a urinary biomarker in human prostate cancer

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Abstract
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 β15 (Tβ15) has been linked to an aggressive CaP phenotype and correlated with future tumor recurrence. We hypothesized that Tβ15 may have clinical utility in biological fluids. METHODS Tβ15 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 Tβ15 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)/(μg_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 Tβ15 above the threshold was significantly higher than normal and genitourinary disease controls (P < 0.001). RP caused urinary Tβ15 to drop significantly (P = 0.005). Pre-surgery Tβ15 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 Tβ15 (P = 0.001, 95% CI = 2.8, 51.8). Combining PSA and Tβ15 (PSA > 4, or PSA > 2.5, Tβ15 > 40, or PSA = 2.5, Tβ15 > 90) provided the same sensitivity as a 2.5 ng/ml PSA cutoff, but markedly improved diagnostic specificity. CONCLUSIONS We report that Tβ15 is a urinary biomarker for CaP and suggest that Tβ15, in combination with PSA, can be used to improve both the sensitivity and specificity of CaP diagnosis.