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

基于基因表达的肾癌复发预测模型。

基本信息

批准号：
16591610
负责人：
YAO Masahiro
金额：
$ 2.3万
依托单位：
Yokohama City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591610/
关键词：
renal carcinoma ADFP gene expression microarray real-time PCR VCAM1 prognosis NNMT

项目摘要

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

使用高密度寡核苷酸微阵列检查了33个肾细胞癌（RCC）和9个正常肾样品的基因表达谱，以试图鉴定肿瘤亚型诊断的生物分子标记物以及预测预测。分层聚类表明，透明细胞RCC，铬虫RCC和正常肾脏组织显示出独特的基因表达谱。 12500个基因中149个基因的平均表达水平在透明电池RCC中的平均表达水平高三倍以上。在其表达在清晰的RCC中上调的基因中，选择了与脂肪分化相关的蛋白（ADFF）进行进一步分析。与微阵列的结果一致，在透明电池RCC中发现ADFP mRNA水平的升高比使用实时定量PCR更频繁地在清晰的RCC中发现了较高的ADFP mRNA。 ADFP的免疫组织化学表现出强烈而独特的肿瘤细胞存储……在大多数透明的RCC中，更多的模式。更重要的是，在单变量和多变量分析中，患有较高AFDP mRNA水平的肿瘤的患者的存活率明显更好。 ADFP是一种脂质储存液滴相关的蛋白质，其转录被认为受von Hippel-Lindau/缺氧诱导因子途径的调节。众所周知，透明电池RCC含有丰富的脂质和胆固醇。 VHL失活后ADFP的持续上调可能与透明电池RCC的形态学外观有关。此外，ADFP表达状态可以提供有用的预后信息作为透明RCC的患者的生物分子标记，我们测量了肿瘤组织中的VCAM1表达水平，并评估了其在肾细胞癌中其意义和预后效用。与正常的肾脏样品相比，在透明细胞RCC和乳头状RCC中显着上调了VCAM1，而在铬虫RCC和Oncocytoma中则下调。在清晰的细胞RCC中，VCAM1表达水平显然很高，症状表现阴性，小肿瘤大小，低阶段，低度，微血管浸润阴性和VIII，改变，改变，改变肿瘤。单变量分析表明，VCAM1高表达与透明细胞和乳头状RCC的更好结果密切相关。此外，COX多变量分析模型与分类样本方法结合表明，这种关联仍然很重要，尤其是在治愈手术切除后清除细胞RCC的患者的无癌生存中。发现VCAM1表达水平在肾肿瘤中是组织学亚型特异性的。将VCAM1表达水平作为生物标志物的确定可以为清晰细胞RCC患者提供有用的预后信息。较少的