Cystatin B as a tissue and urinary biomarker of bladder cancer recurrence and disease progression.
Cystatin B as a tissue and urinary biomarker of bladder cancer recurrence and disease progression.
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DOI：
10.1158/1078-0432.ccr-08-1143
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发表时间：
2009-02-01
期刊：
影响因子：
--
通讯作者：
Zetter BR
中科院分区：
文献类型：
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作者：
Feldman AS;Banyard J;Wu CL;McDougal WS;Zetter BR
利用蛋白质组学技术，我们试图从移行细胞癌（TCC）患者的组织和尿液中鉴定新的蛋白质生物标志物。尿和组织蛋白质组进行了分析和差异表达的蛋白质鉴定质谱。其中一种蛋白质，胱抑素B，在TCC组织中通过免疫组织化学和在尿中通过半定量蛋白质印迹分析进一步分析。胱抑素B组织染色强度与TCC分级显著一致地增加（p=0.0008）。尿胱抑素B水平升高与肿瘤分级（p=0.062）和分期（p=0.0047）增加相关。胱抑素B水平升高的患者至疾病复发的平均时间（12个月，SE 1.82）短于胱抑素水平较低的患者（28.8个月，SE 2.26），p=0.0047。同样，与尿胱抑素B水平低的患者相比，胱抑素B水平升高的患者至分级/分期进展的时间更短（p=0.0007）。通过多变量考克斯回归分析，半胱氨酸蛋白酶抑制剂B水平升高是预测疾病复发（HR 3.8，95%CI 1.5-9.5，p=0.0049）和分级/分期进展（HR 10.4，95%CI 1.6-201.5，p=0.0104）的最重要变量。胱抑素B在膀胱癌患者的组织和尿液中升高。尿半胱氨酸蛋白酶抑制剂B水平与肿瘤分级、分期正相关，并且与疾病复发和进展的较短时间正相关。因此，半胱氨酸蛋白酶抑制剂B可能是一种新的预测膀胱TCC的生物标志物。
Using proteomic techniques, we sought to identify novel protein biomarkers in tissue and urine from patients with transitional cell carcinoma (TCC). Urinary and tissue proteomes were analyzed and differentially expressed proteins identified by mass spectrometry. One of the proteins, cystatin B, was further analyzed in TCC tissue by immunohistochemistry and in urine by semiquantitative western blot analysis. Cystatin B tissue staining intensity significantly increased concordantly with TCC grade (p=0.0008). Elevated urinary cystatin B levels correlated with increasing tumor grade (p=0.062) and stage (p=0.0047). Patients with elevated levels of cystatin B had a shorter mean time to disease recurrence (12 months, SE 1.82) compared to patients who had low levels (28.8 months, SE 2.26), p=0.0047. Similarly, patients with elevated cystatin B levels had a shorter time to grade/stage progression, compared to patients with low urinary cystatin B (p=0.0007). By multivariate Cox regression analysis, an elevated cystatin B level was the most significant variable predicting disease recurrence (HR 3.8, 95% CI 1.5–9.5, p=0.0049) and grade/stage progression (HR 10.4, 95% CI 1.6–201.5, p=0.0104). Cystatin B is elevated in tissue and urine of bladder cancer patients. Cystatin B urine levels are positively correlated with tumor grade, stage, and with shorter time to disease recurrence and progression. Consequently cystatin B may be useful as a novel predictive biomarker in TCC of the bladder.