Ebbing Jan, Mathia Susanne, Seibert Felix S, Pagonas Nikolaos, Bauer Frederic, Erber Barbara, Günzel Karsten, Kilic Ergin, Kempkensteffen Carsten, Miller Kurt, Bachmann Alexander, Rosenberger Christian, Zidek Walter, Westhoff Timm H
Department of Urology, Charité, Campus Benjamin Franklin, Berlin, Germany.
World J Urol. 2014 Dec;32(6):1485-92. doi: 10.1007/s00345-013-1227-8. Epub 2013 Dec 31.
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.
最近，一项对膀胱癌患者血清的蛋白质组学研究将S100A8和S100A9鉴定为肿瘤相关蛋白。本横断面研究调查了钙卫蛋白（S100A8/S100A9的异二聚体）是否可作为检测尿路上皮膀胱癌的尿液生物标志物。
对181名受试者进行了尿钙卫蛋白浓度评估，其中包括46例膀胱癌患者。41例肾细胞癌患者、54例前列腺癌患者和40名健康受试者作为对照。急性肾损伤、尿路感染、既往卡介苗治疗和膀胱肿瘤二次经尿道切除术被定义为排除标准。通过酶联免疫吸附测定和检测钙卫蛋白的免疫组织化学进行评估。
膀胱癌患者的钙卫蛋白浓度中位数（ng/ml）显著高于健康对照组（522.3对51.0，p<0.001）、肾细胞癌患者（90.4，p<0.001）和前列腺癌患者（71.8，p<0.001）。在尿路上皮癌中，肿瘤细胞的一个亚群和浸润的髓样细胞中出现明显的免疫染色。受试者工作特征分析显示，区分膀胱癌和健康对照的曲线下面积为0.88。由约登指数确定的临界值为140 ng/ml，敏感性和特异性值分别为80.4%和92.5%。低级别肿瘤的钙卫蛋白浓度显著低于高级别肿瘤（351.9对1635.2 ng/ml，p=0.004）。
尿路上皮恶性肿瘤与尿液中钙卫蛋白浓度的高度升高有关。在没有肾衰竭和脓尿的情况下，钙卫蛋白是检测膀胱癌的一个有前景的生物标志物。
