Liou Louis S, Shi Ting, Duan Zhong-Hui, Sadhukhan Provash, Der Sandy D, Novick Andrew A, Hissong John, Skacel Marek, Almasan Alexandru, DiDonato Joseph A
Department of Cancer Biology, Cleveland Clinic Foundation, Cleveland, USA.
BMC Urol. 2004 Jun 22;4:9. doi: 10.1186/1471-2490-4-9.
Renal cell carcinoma (RCC) is the most common cancer in adult kidney. The accuracy of current diagnosis and prognosis of the disease and the effectiveness of the treatment for the disease are limited by the poor understanding of the disease at the molecular level. To better understand the genetics and biology of RCC, we profiled the expression of 7,129 genes in both clear cell RCC tissue and cell lines using oligonucleotide arrays.
Total RNAs isolated from renal cell tumors, adjacent normal tissue and metastatic RCC cell lines were hybridized to affymatrix HuFL oligonucleotide arrays. Genes were categorized into different functional groups based on the description of the Gene Ontology Consortium and analyzed based on the gene expression levels. Gene expression profiles of the tissue and cell line samples were visualized and classified by singular value decomposition. Reverse transcription polymerase chain reaction was performed to confirm the expression alterations of selected genes in RCC.
Selected genes were annotated based on biological processes and clustered into functional groups. The expression levels of genes in each group were also analyzed. Seventy-four commonly differentially expressed genes with more than five-fold changes in RCC tissues were identified. The expression alterations of selected genes from these seventy-four genes were further verified using reverse transcription polymerase chain reaction (RT-PCR). Detailed comparison of gene expression patterns in RCC tissue and RCC cell lines shows significant differences between the two types of samples, but many important expression patterns were preserved.
This is one of the initial studies that examine the functional ontology of a large number of genes in RCC. Extensive annotation, clustering and analysis of a large number of genes based on the gene functional ontology revealed many interesting gene expression patterns in RCC. Most notably, genes involved in cell adhesion were dominantly up-regulated whereas genes involved in transport were dominantly down-regulated. This study reveals significant gene expression alterations in key biological pathways and provides potential insights into understanding the molecular mechanism of renal cell carcinogenesis.
肾细胞癌（RCC）是成人肾脏中最常见的癌症。目前对该疾病的诊断和预后准确性以及治疗效果受到在分子水平上对该疾病了解不足的限制。为了更好地理解RCC的遗传学和生物学特性，我们使用寡核苷酸阵列分析了7129个基因在透明细胞RCC组织和细胞系中的表达情况。
从肾细胞肿瘤、相邻正常组织和转移性RCC细胞系中分离出的总RNA与Affymatrix HuFL寡核苷酸阵列进行杂交。根据基因本体联合会的描述将基因分类到不同的功能组，并基于基因表达水平进行分析。通过奇异值分解对组织和细胞系样本的基因表达谱进行可视化和分类。进行逆转录聚合酶链反应以确认RCC中选定基因的表达变化。
选定的基因根据生物学过程进行注释并聚类到功能组中。还分析了每组中基因的表达水平。在RCC组织中鉴定出74个常见的差异表达基因，其变化超过五倍。使用逆转录聚合酶链反应（RT-PCR）进一步验证了这74个基因中选定基因的表达变化。RCC组织和RCC细胞系中基因表达模式的详细比较显示这两种类型的样本之间存在显著差异，但许多重要的表达模式得以保留。
这是最初研究RCC中大量基因功能本体的研究之一。基于基因功能本体对大量基因进行广泛注释、聚类和分析，揭示了RCC中许多有趣的基因表达模式。最值得注意的是，参与细胞黏附的基因主要上调，而参与转运的基因主要下调。本研究揭示了关键生物学途径中的显著基因表达变化，并为理解肾细胞癌发生的分子机制提供了潜在的见解。
