Celis J E, Rasmussen H H, Vorum H, Madsen P, Honoré B, Wolf H, Orntoft T F
Department of Medical Biochemistry, University of Aarhus, Denmark.
J Urol. 1996 Jun;155(6):2105-12.
To report a single biomarker, psoriasin (Mr 11.0 kd, pI 6.2), a calcium binding protein which is expressed largely by stratified squamous epithelia and is externalized to the urine of bladder squamous cell carcinoma (SCC) bearing patients.
Protein expression profiles of SCCs obtained immediately after surgery were analyzed by two-dimensional gel electrophoresis and Coomassie blue staining. Protein identity was determined by microsequencing and immunoblotting. Protein expression in cryosections was studied by immunofluorescence.
Four patients with SCC were identified from 100 samples of patients with suspected transitional cell carcinoma (TCC). The protein profiles of the 4 SCCs (56-1, grade III, T4; 181-1, grade I, T3; 219-1, grade III, T3 and 239-1, grade not determined, T2-4) resembled that of keratinocytes, suggesting that these cells express an early developmental pattern of gene expression. Besides expressing markers characteristic of keratinizing stratified squamous epithelia, the SCCs exhibited psoriasin, a protein externalized to the medium by keratinocytes. Immunohistochemistry of 3 of the SCCs with psoriasin antibodies showed that the positive cells were confined chiefly to the "squamous pearls." The presence of psoriasin in the urine of the 4 SCC patients was demonstrated by two-dimensional gel immunoblotting. Similar analysis of 43 urines from patients with bladder tumors other than SCC revealed 7 positives, some of which may reflect squamous differentiation. Analysis of the urine of 13 control individuals (12 males matched by age and a 42-year-old female) revealed 2 positives. Immunoblotting of the SCC patients' serum proteins with psoriasin antibodies failed to reveal the protein.
The results point towards psoriasin, alone or as part of a biomarker profile, as a potential marker for the noninvasive follow-up of patients with SCC.
报告一种单一生物标志物——牛皮癣素（分子量11.0 kd，等电点6.2），一种钙结合蛋白，主要由复层鳞状上皮表达，并在膀胱鳞状细胞癌（SCC）患者的尿液中出现。
通过二维凝胶电泳和考马斯亮蓝染色分析术后立即获取的SCC的蛋白质表达谱。通过微量测序和免疫印迹确定蛋白质身份。通过免疫荧光研究冰冻切片中的蛋白质表达。
从100例疑似移行细胞癌（TCC）患者的样本中鉴定出4例SCC患者。这4例SCC（56 - 1，III级，T4；181 - 1，I级，T3；219 - 1，III级，T3和239 - 1，分级未确定，T2 - 4）的蛋白质谱类似于角质形成细胞，表明这些细胞表达早期发育模式的基因表达。除了表达角质化复层鳞状上皮的特征性标志物外，SCC还表现出牛皮癣素，一种由角质形成细胞分泌到培养基中的蛋白质。用牛皮癣素抗体对其中3例SCC进行免疫组织化学分析表明，阳性细胞主要局限于“鳞状珠”。通过二维凝胶免疫印迹证明4例SCC患者尿液中存在牛皮癣素。对43例非SCC膀胱肿瘤患者的尿液进行类似分析发现7例阳性，其中一些可能反映鳞状分化。对13名对照个体（12名年龄匹配的男性和一名42岁女性）的尿液分析发现2例阳性。用牛皮癣素抗体对SCC患者的血清蛋白进行免疫印迹未发现该蛋白。
结果表明牛皮癣素单独或作为生物标志物谱的一部分，作为SCC患者无创随访的潜在标志物。
