Urinary calprotectin: a new diagnostic marker in urothelial carcinoma of the bladder
Urinary calprotectin: a new diagnostic marker in urothelial carcinoma of the bladder
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DOI：
10.1007/s00345-013-1227-8
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发表时间：
2014-12-01
影响因子：
3.4
通讯作者：
Westhoff, Timm H.
中科院分区：
文献类型：
--
作者：
Ebbing, Jan;Mathia, Susanne;Westhoff, Timm H.
最近，一项膀胱癌患者血清的蛋白质组学研究发现S100A8和S100A9是肿瘤相关蛋白。本横断研究探讨钙保护蛋白（S100A8/S100A9的异源二聚体）是否可以作为尿路上皮性膀胱癌检测的尿液生物标志物。在包括46例膀胱癌患者在内的181名受试者中评估尿钙保护蛋白浓度。选取肾细胞癌41例，前列腺癌54例，健康对照40例。排除标准为急性肾损伤、尿路感染、既往bcg治疗和继发经尿道膀胱肿瘤切除术。采用酶联免疫吸附法和免疫组化法检测钙保护蛋白。膀胱癌患者钙保护蛋白中位浓度（ng/ml）显著高于健康对照组（522.3 vs. 51.0, p < 0.001）、肾癌患者（90.4,p < 0.001）和前列腺癌患者（71.8,p < 0.001）。在尿路上皮癌中，有一部分肿瘤细胞和浸润性髓细胞出现明显的免疫染色。受试者工作特征分析为膀胱癌与健康对照的鉴别曲线下面积为0.88。截断值为140 ng/ml（由约登指数确定），敏感性和特异性分别为80.4%和92.5%。低级别肿瘤的钙保护蛋白浓度明显低于高级别肿瘤（351.9 vs 1635.2 ng/ml, p = 0.004）。尿路上皮恶性肿瘤与尿中钙护蛋白浓度增高有关。在没有肾衰竭和脓尿的情况下，钙保护蛋白是一种很有前途的膀胱癌检测生物标志物。
Recently, a proteomic study of sera from patients with bladder cancer identified S100A8 and S100A9 as tumor-associated proteins. The present cross-sectional study investigates whether calprotectin, the heterodimer of S100A8/S100A9 may serve as a urinary biomarker for the detection of urothelial bladder cancer.Urinary calprotectin concentrations were assessed in a population of 181 subjects including 46 cases of bladder cancer. 41 cases of renal cell cancer, 54 cases of prostate cancer, and 40 healthy subjects served as control. Acute kidney injury, urinary tract infection, previous BCG-treatment and secondary transurethral resection of the bladder tumor were defined as exclusion criteria. Assessment was performed by enzyme-linked immunosorbent assay and immunohistochemistry detecting calprotectin.Median calprotectin concentrations (ng/ml) were significantly higher in patients with bladder cancer than in healthy controls (522.3 vs. 51.0, p < 0.001), renal cell cancer (90.4, p < 0.001), and prostate cancer (71.8, p < 0.001). In urothelial carcinoma prominent immunostaining occurred in a subset of tumor cells and in infiltrating myeloid cells. Receiver operating characteristic analysis provided an area under the curve of 0.88 for the differentiation of bladder cancer and healthy control. A cut-off value of 140 ng/ml (determined by Youden's index) resulted in sensitivity and specificity values of 80.4 and 92.5 %. Low grade tumors were associated with significantly lower calprotectin concentrations than high grade tumors (351.9 vs. 1635.2 ng/ml, p = 0.004).Urothelial malignancies are associated with highly increased concentrations of calprotecin in the urine. In absence of renal failure and pyuria, calprotectin constitutes a promising biomarker for the detection of bladder cancer.