Han Won K, Alinani Anwar, Wu Chin-Lee, Michaelson Dror, Loda Massimo, McGovern Francis J, Thadhani Ravi, Bonventre Joseph V
Renal Division, Brigham and Women's Hospital, Medical Service, Massachusetts General Hospital, Boston, USA.
J Am Soc Nephrol. 2005 Apr;16(4):1126-34. doi: 10.1681/ASN.2004070530. Epub 2005 Mar 2.
Human kidney injury molecule-1 (hKIM-1) is a type 1 transmembrane protein that is not detectable in normal kidney tissue but is expressed at high levels in human and rodent kidneys with dedifferentiated proximal tubule epithelial cells after ischemic or toxic injury. Therefore, it was hypothesized that renal tumors express hKIM-1 and release this protein into the urine. Forty renal cell carcinoma (RCC) and 484 nonrenal tumors were analyzed by immunohistochemistry for expression of hKIM-1 (group 1). Urine samples before nephrectomy and nephrectomy tissue samples were collected from an additional 42 patients with renal tumors, from 30 normal control subjects, and also from 10 patients with prostate carcinoma (group 2). In five additional patients with RCC, urine was collected before and after nephrectomy (group 3). Tissue was examined for expression of hKIM-1, and cell-free urine supernatants were analyzed for hKIM-1 by ELISA. Urinary hKIM-1 was normalized to the urinary creatinine concentration (U(Cr)). Expression of hKIM-1 was present in 32 tissue sections (91%) of 35 clear cell RCC (group 1). In group 2, the normalized urinary hKIM-1 levels were significantly higher in patients with clear cell RCC (0.39 +/- 0.08 ng/mg U(Cr); n = 21), compared with levels in patients with prostate carcinoma (0.12 +/- 0.03 ng/mg U(Cr); P < 0.02; n = 10), or normal control subjects (0.05 +/- 0.01 ng/mg U(Cr); P < 0.005; n = 30). Tissue sections from 28 (82%) of 34 primary RCC stained positively for the expression of hKIM-1. In all patients with a detectable prenephrectomy urinary hKIM-1 level, there was either complete disappearance or marked reduction after nephrectomy (group 3). In conclusion, the cleaved ectodomain of hKIM-1 can be detected in the urine of patients with RCC and may serve as a new biomarker for early detection of RCC.
人肾损伤分子-1（hKIM-1）是一种1型跨膜蛋白，在正常肾组织中无法检测到，但在缺血或毒性损伤后近端肾小管上皮细胞去分化的人和啮齿动物肾脏中高表达。因此，有人推测肾肿瘤表达hKIM-1并将这种蛋白释放到尿液中。通过免疫组织化学分析了40例肾细胞癌（RCC）和484例非肾肿瘤中hKIM-1的表达情况（第1组）。另外从42例肾肿瘤患者、30例正常对照者以及10例前列腺癌患者中收集了肾切除术前的尿液样本和肾切除组织样本（第2组）。在另外5例RCC患者中，收集了肾切除术前和术后的尿液（第3组）。检测组织中hKIM-1的表达，并通过酶联免疫吸附测定（ELISA）分析无细胞尿液上清液中的hKIM-1。将尿hKIM-1标准化为尿肌酐浓度（U（Cr））。在35例透明细胞RCC的32个组织切片（91%）中存在hKIM-1表达（第1组）。在第2组中，透明细胞RCC患者的标准化尿hKIM-1水平（0.39±0.08 ng/mg U（Cr）；n = 21）显著高于前列腺癌患者（0.12±0.03 ng/mg U（Cr）；P < 0.02；n = 10）或正常对照者（0.05±0.01 ng/mg U（Cr）；P < 0.005；n = 30）。34例原发性RCC中的28例（82%）组织切片hKIM-1表达呈阳性。在所有术前尿hKIM-1水平可检测到的患者中，肾切除术后该水平要么完全消失要么显著降低（第3组）。总之，在RCC患者的尿液中可检测到hKIM-1的裂解胞外域，其可能作为RCC早期检测的一种新生物标志物。
