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

采用高密度寡核苷酸芯片检测33例肾细胞癌（RCC）和9例正常肾组织的基因表达谱，以寻找诊断肿瘤亚型和预测预后的生物分子标记物。层次聚类分析表明，透明细胞肾细胞癌，嫌色细胞肾细胞癌和正常肾组织显示出独特的基因表达谱。透明细胞肾细胞癌中12500个基因中有149个基因的平均表达水平是嫌色细胞肾细胞癌和正常肾组织的3倍多。在透明细胞肾细胞癌中表达上调的基因中，选择脂肪分化相关蛋白（ADFF）进行进一步分析。与微阵列的结果一致，使用实时定量PCR发现透明细胞RCC中ADFP mRNA水平的增加比其他非透明细胞肿瘤亚型更频繁。ADFP免疫组化显示强烈和独特的肿瘤细胞染色 ...更多信息 大多数透明细胞RCC的模式。更重要的是，在单变量和多变量分析中，AFDP mRNA水平较高的肿瘤患者的生存率明显更高。ADFP是一种脂质储存液滴相关蛋白，其转录被认为是由von Hippel-Lindau/缺氧诱导因子途径调节的。已知透明细胞肾细胞癌含有丰富的脂质和胆固醇。因此，这是可能的，持续上调ADFP后VHL失活参与透明细胞肾细胞癌的形态外观。此外，ADFP的表达状态可能提供有用的预后信息，作为一个生物分子标记物在透明细胞肾细胞癌患者。接下来，我们测量VCAM 1在肿瘤组织中的表达水平，并评估其意义和预后效用在肾细胞癌。与正常肾组织相比，VCAM 1在透明细胞肾细胞癌和乳头状肾细胞癌中表达显著上调，而在嫌色细胞肾细胞癌和嗜酸细胞瘤中表达下调。在透明细胞肾细胞癌中，VCAM 1的表达水平在症状表现阴性、肿瘤体积小、低分期、低级别、微血管浸润阴性和VIII、变异阳性的肿瘤中明显较高。单变量分析表明，VCAM 1高表达与透明细胞和乳头状RCC的预后良好密切相关。此外，结合分裂样本方法的考克斯多变量分析模型显示，这种关联仍然是显着的，特别是在透明细胞肾细胞癌患者根治性手术切除后的无癌生存。VCAM 1的表达水平在肾肿瘤中具有组织学亚型特异性。VCAM 1表达水平作为生物标志物的测定可以为透明细胞RCC患者提供有用的预后信息。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