Gene expression analysis of renal carcinoma: adipose differentiation-related protein as a potential diagnostic and prognostic biomarker for clear-cell renal carcinoma
Gene expression analysis of renal carcinoma: adipose differentiation-related protein as a potential diagnostic and prognostic biomarker for clear-cell renal carcinoma
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DOI：
10.1002/path.1693
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发表时间：
2005-02-01
影响因子：
7.3
通讯作者：
Kubota, Y
中科院分区：
文献类型：
--
作者：
Yao, M;Tabuchi, H;Kubota, Y
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，试图鉴定用于诊断肿瘤亚型和预测预后的生物分子标记。层次聚类表明透明细胞肾细胞癌、嫌色细胞肾细胞癌和正常肾组织表现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 个的平均表达水平比嫌色肾细胞癌和正常肾组织高出三倍多。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（ADFP）和烟酰胺N-甲基转移酶（NNMT）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 和 NNMT mRNA 水平升高的频率高于其他非透明细胞肿瘤亚型。 ADFP 的免疫组织化学显示大多数透明细胞肾细胞癌中具有强烈且独特的肿瘤细胞染色模式。更重要的是，在单变量和多变量分析中，具有较高 AFDP mRNA 水平的肿瘤患者的生存率均显着提高。 ADFP 是一种脂质储存液滴相关蛋白，其转录被认为受 von Hippel-Lindau/缺氧诱导因子途径调节。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 的持续上调可能与透明细胞肾细胞癌的形态学外观有关。此外，ADFP 表达状态可以作为透明细胞肾细胞癌患者的生物分子标记物提供有用的预后信息。版权所有 (C) 2005 大不列颠及爱尔兰病理学会。约翰·威利儿子有限公司出版
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 tumour 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 upregulated in clear-cell RCC, adipose differentiation-related protein (ADFP) and nicotinamide N-methyltransferase (NNMT) were selected for further analysis. Consistent with the results of the microarray, increased levels of ADFP and NNMT mRNA were found more frequently in clear-cell RCCs than in other non-clear-cell tumour subtypes using real-time quantitative PCR. Immunohistochemistry for ADFP showed strong and unique tumour cell staining patterns in the majority of clear-cell RCCs. More importantly, patients bearing tumours 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 upregulation 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 biornolecular marker in patients with clear-cell RCC. Copyright (C) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley Sons, Ltd.