Prediction Model for Renal Carcinoma Recurrence based on the Gene Expressions.

应用高密度寡核苷酸芯片检测了33例肾细胞癌(RCC)和9例正常肾组织的基因表达谱，试图寻找用于诊断肿瘤亚型和预测预后的生物分子标志物。系统聚类法显示透明细胞肾细胞癌、嫌色肾细胞癌和正常肾组织表现出不同的基因表达谱。在12500个基因中，有149个在透明细胞肾癌中的平均表达水平是嫌色肾癌和正常肾组织的3倍以上。在透明细胞肾癌中表达上调的基因中，脂肪分化相关蛋白(ADFF)被选作进一步分析。与芯片结果一致的是，实时定量聚合酶链式反应发现，在透明细胞肾癌中，ADFP mRNA的表达水平比在其他非透明细胞肿瘤亚型中更常见。ADFP免疫组织化学显示肿瘤细胞…染色强烈且独特大多数透明细胞RCC中有更多的模式。更重要的是，在单变量和多变量分析中，AFDP信使核糖核酸水平较高的肿瘤患者的存活率显著提高。ADFP是一种脂滴相关蛋白，其转录受von Hippel-Lindau/低氧诱导因子途径的调控。众所周知，透明细胞肾细胞癌含有丰富的脂质和胆固醇。因此，VHL失活后ADFP的持续上调很可能与透明细胞肾癌的形态特征有关。此外，ADFP的表达状况可能为肾细胞癌患者提供有用的预后信息，作为生物分子标志物。接下来，我们检测了肿瘤组织中VCAM1的表达水平，并评估其在肾癌中的意义和预后价值。与正常肾组织相比，VCAM1在透明细胞肾细胞癌和乳头状肾细胞癌中表达显著上调，而在嫌色肾癌和嗜酸细胞瘤中表达下调。在透明细胞肾癌中，VCAM1在有症状阴性、肿瘤体积小、低分期、低级别、微血管侵犯阴性和VIII型改变阳性的肿瘤中的表达水平明显升高。单变量分析表明，VCAM1高表达与透明细胞和乳头状肾细胞癌预后良好密切相关。进一步，结合分裂样本法的COX多变量分析模型显示，这种关联仍然显著，特别是在透明细胞肾癌根治性手术切除后的无癌生存率方面。VCAM1在肾肿瘤中的表达水平在组织学上具有亚型特异性。作为生物标志物的VCAM1表达水平的测定可为透明细胞肾癌患者提供有用的预后信息。较少

The gene expression profiles of 33 renal cell carcinomas (RCCs) and nine normal kidney samples were examined using high-density oligonucleotide microarrays in an attempt to identify biomolecular markers for the diagnosis of tumor subtypes and also for prediction of prognosis. Hierarchical clustering demonstrated that clear-cell RCC, chromophobe RCC, and normal kidney tissue showed distinctive gene expression profiles. The mean expression levels of 149 of 12500 genes were more than three times higher in clear-cell RCC than in chromophobe RCC and normal kidney tissue. Among the genes whose expression was up-regulated in clear-cell RCC, adipose differentiation-related protein (ADFF) was selected for further analysis. Consistent with the results of the microarray, increased levels of ADFP mRNA were found more frequently in clear-cell RCCs than in other non-clear-cell tumor subtypes using real-time quantitative PCR. Immunohistochemistry for ADFP showed strong and unique tumor cell staining … More patterns in the majority of clear-cell RCCs. More importantly, patients bearing tumors with higher AFDP mRNA levels showed significantly better survival in both univariate and multivariate analyses. ADFP is a lipid storage droplet-associated protein and its transcription is considered to be regulated by the von Hippel-Lindau/hypoxia-inducible factor pathway. It is known that clear-cell RCC contains abundant lipids and cholesterols. Thus it is likely that sustained up-regulation of ADFP following VHL inactivation is involved in the morphological appearance of clear-cell RCC. Moreover ADFP expression status may provide useful prognostic information as a biomolecular marker in patients with clear-cell RCC.Next, we measured VCAM1 expression levels in tumor tissues and evaluated its significance and prognostic utility in renal cell carcinoma. In comparison with normal kidney samples, VCAM1 was significantly up-regulated in clear cell RCC and papillary RCC, while it was down-regulated in chromophobe RCC and oncocytoma. In clear cell RCC, VCAM1 expression levels were apparently high in symptomatic presentation-negative, small tumor size, low-stage, low-grade, microvascular invasion-negative, and VIII, alteration-positive tumors. Univariate analyses demonstrated that VCAM1 high expression is strongly associated with better outcomes in clear cell and papillary RCCs. Further, Cox multivariate analysis models combined with the split-sample method revealed that this association is still significant, especially in cancer-free survival for patients with clear cell RCC after curative surgical resection. VCAM1 expression levels were found to be histologically subtype-specific in renal tumors. Determination of the VCAM1 expression level as a biomarker can provide useful prognostic information for patients with clear cell RCC. Less