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 个正常肾脏样本的基因表达谱，试图识别用于诊断肿瘤亚型和预测预后的生物分子标记。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。12500 个基因中有 149 个的平均表达水平是其三倍以上。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，这与嫌色肾细胞癌和正常肾组织的结果一致。微阵列中，使用实时定量 PCR 检测 ADFP 的免疫组织化学显示，透明细胞肾细胞癌中 ADFP mRNA 水平的增加比其他非透明细胞肿瘤亚型更常见。大多数透明细胞肾细胞癌中的细胞染色模式更重要的是，具有较高 AFDP mRNA 水平的肿瘤患者在单变量和多变量分析中均显示出明显更好的生存率，ADFP 是一种脂质储存液滴相关蛋白，其转录被认为是。受到 von Hippel-Lindau/缺氧诱导因子途径的调节已知透明细胞 RCC 含有丰富的脂质和胆固醇，因此 ADFP 可能在 VHL 后持续上调。此外，ADFP 的表达状态可能作为透明细胞 RCC 患者的生物分子标志物提供有用的预后信息。接下来，我们测量了肿瘤组织中 VCAM1 的表达水平并评估了其意义和预后。与正常肾脏样本相比，VCAM1 在透明细胞 RCC 和乳头状 RCC 中显着上调，而在嫌色细胞 RCC 和乳头状 RCC 中下调。在透明细胞肾细胞癌中，VCAM1 表达水平在症状表现阴性、小肿瘤、低阶段、低级别、微血管侵袭阴性和 VIII、改变阳性肿瘤中明显较高。表达与透明细胞和乳头状肾细胞癌的更好结果密切相关，此外，Cox 多变量分析模型结合分割样本方法显示，这种关联仍然很重要，特别是在透明细胞肾细胞癌患者的无癌生存方面。根治性手术切除后，发现肾肿瘤中的 VCAM1 表达水平具有组织学亚型特异性，测定 VCAM1 表达水平作为生物标志物可以为透明细胞肾细胞癌患者提供有用的预后信息。