Use of thymosin beta15 as a urinary biomarker in human prostate cancer.

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. 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. 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. 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. (c) 2005 Wiley-Liss, Inc.

胸腺素β15在人前列腺癌中作为尿生物标志物的用途。

需要额外的前列腺癌(CaP)生物标志物来增加诊断的准确性和识别有复发风险的患者。在基于组织的测定中，胸腺素β15(tβ15)与侵袭性CaP表型相关，并与未来肿瘤复发相关。我们假设Tbeta15可能在生物液体中具有临床效用。在CaP患者的尿液中测量Tbeta15未治疗组(N = 61)、前列腺切除术组(RP，N = 46)、雄激素剥夺治疗组(ADT，N = 14)和对照组；正常(N = 52)、泌尿生殖系统癌(N = 15)、非恶性前列腺疾病(N = 81)和其他泌尿外科疾病(N = 73)。我们评估了尿Tbeta15单独或与前列腺特异性抗原(PSA)联合用于CaP诊断的效用，以及与CaP进展的关系。使用受试者操作特征分析定义了40(ng/dl)/(mug _ protein/mg _肌酐)的正常阈值，并标记为年龄匹配对照组的第19个百分位数。尿Tbeta15高于阈值的未治疗CaP患者的比例显著高于正常和泌尿生殖系统疾病对照组(P & lt0.001).RP导致尿Tbeta15显著下降(P = 0.005)。术前Tbeta15浓度高于正常阈值可能会增加CaP复发的风险。与正常对照组相比，接受ADT治疗的侵袭性CaP患者尿Tbeta15升高的可能性是正常对照组的12倍(P = 0.001，95% CI = 2.8，51.8)。组合PSA和tbeta 15(PSA & gt；4，或PSA & gt2.5，Tbeta15 & gt40，或者PSA = 2.5，Tbeta15 & gt90)提供了与2.5 ng/ml PSA临界值相同的灵敏度，但显著提高了诊断特异性。我们报道Tbeta15是CaP的尿生物标志物，并建议Tbeta15与PSA联合使用可用于提高CaP诊断的敏感性和特异性。(c) 2005年威利利斯公司。