Vasudev N S, Sim S, Cairns D A, Ferguson R E, Craven R A, Stanley A, Cartledge J, Thompson D, Selby P J, Banks R E
Cancer Research UK Clinical Centre, Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, UK.
Br J Cancer. 2009 Oct 6;101(7):1175-82. doi: 10.1038/sj.bjc.6605250.
No circulating markers are routinely used for renal cancer. The objective of this pilot study was to investigate whether conditioned media (CM) from renal cancer cell lines contains potential biomarkers that, when measured in clinical fluids, have diagnostic or prognostic utility.
Comparative 2D PAGE profiling of CM from renal cell carcinoma (RCC) and normal renal cultures identified cathepsin D that was subsequently validated in urine samples from 239 patients and healthy and benign disease subjects.
Urinary cathepsin D was found to be significantly associated with overall (OS) (hazard ratio, HR, 1.33, 95%CI [1.09-1.63], P=0.005) and cancer-specific survival (HR 1.36, 95%CI [1.07-1.74], P=0.013) in RCC patients on univariate analysis. An optimal cut point (211 ng ml(-1) micromolCr(-1)) around which to stratify patients by OS was determined. Five-year OS equal to/above and below this value was 47.0% (95%CI 35.4%, 62.4%) and 60.9% (48.8%, 76.0%), respectively. On multivariable analysis using pre-operative variables, cathepsin D showed some evidence of independent prognostic value for OS (likelihood ratio test P-value=0.056) although requiring further validation in larger patient numbers with sufficient statistical power to determine independent significance.
These data establish an important proof of principle and show the potential of proteomics-based studies. Cathepsin D may be of value as a pre-operative urinary biomarker for RCC, alone or in combination.
目前尚无用于肾癌的常规循环标志物。本初步研究的目的是调查肾癌细胞系的条件培养基（CM）中是否含有潜在的生物标志物，这些标志物在临床体液中检测时具有诊断或预后价值。
对肾细胞癌（RCC）和正常肾培养物的CM进行二维聚丙烯酰胺凝胶电泳（2D PAGE）比较分析，鉴定出组织蛋白酶D，随后在239例患者以及健康和良性疾病受试者的尿液样本中进行验证。
在单变量分析中，发现RCC患者尿液中的组织蛋白酶D与总生存期（OS）（风险比，HR，1.33，95%可信区间[1.09 - 1.63]，P = 0.005）和癌症特异性生存期（HR 1.36，95%可信区间[1.07 - 1.74]，P = 0.013）显著相关。确定了一个最佳切点（211 ng ml(-1) micromolCr(-1)），用于根据OS对患者进行分层。OS等于或高于和低于该值的五年生存率分别为47.0%（95%可信区间35.4%，62.4%）和60.9%（48.8%，76.0%）。在使用术前变量的多变量分析中，组织蛋白酶D显示出对OS具有独立预后价值的一些证据（似然比检验P值 = 0.056），尽管需要在更多患者中进行进一步验证，以确定具有足够统计学效力的独立显著性。
这些数据确立了一个重要的原理证明，并显示了基于蛋白质组学研究的潜力。组织蛋白酶D可能作为RCC术前尿液生物标志物具有价值，单独使用或联合使用均可。
