差异基因表达可识别肾细胞癌的亚组。

Differential gene expression identifies subgroups of renal cell carcinoma.

作者信息

Skubitz Keith M, Zimmermann Wolfgang, Kammerer Robert, Pambuccian Stefan, Skubitz Amy P N

机构信息

Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.

出版信息

J Lab Clin Med. 2006 May;147(5):250-67. doi: 10.1016/j.lab.2006.04.001.

DOI:10.1016/j.lab.2006.04.001

PMID:16697773

Abstract

Clear cell carcinoma of the kidney, the most common subtype of renal cell cancer, displays different biological behavior in different patients. This heterogeneity cannot be recognized by light microscopy. In this study, gene expression in 16 clear cell renal cell carcinoma samples and 17 non-malignant tissue types comprising 539 samples was determined using oligonucleotide microarrays representing approximately 40,000 known genes and ESTs. Differences in gene expression were quantified as the fold change in gene expression between the various sets of samples. A set of genes was identified that was overexpressed in the renal cell carcinoma samples compared with the normal kidney samples. Principle component analysis of the set of renal cell carcinomas using this set of genes overexpressed in renal cell cancer revealed the existence of 2 major subgroups among the renal carcinomas. A series of principle component analyses of the set of renal cell carcinomas using different gene sets composed of genes involved in different metabolic pathways also revealed the same 2 major subgroups of the renal cell cancers. Eisen clustering using the same genes also revealed the same 2 major renal cell cancer subsets. Review of the pathology suggested that these 2 subgroups differed in pathologic grade. Genes differentially expressed between the 2 renal cell cancer subsets were identified. Examination of gene expression in each renal cell cancer subset and the pool of renal cell carcinoma samples compared with that in 17 different normal tissues revealed genes specifically overexpressed in renal cell cancer compared with these normal tissues. The authors conclude that gene expression patterns may be useful in helping to further classify subtypes of renal cell carcinoma that may have clinical significance. In addition, the genes identified as overexpressed in each set of clear cell renal cell carcinomas compared with normal tissues may represent useful targets for therapy.

摘要

肾透明细胞癌是肾细胞癌最常见的亚型，在不同患者中表现出不同的生物学行为。这种异质性无法通过光学显微镜识别。在本研究中，使用代表约40,000个已知基因和EST的寡核苷酸微阵列，测定了16个肾透明细胞癌样本和包括539个样本的17种非恶性组织类型中的基因表达。基因表达差异以不同样本组之间基因表达的倍数变化来量化。鉴定出一组在肾细胞癌样本中相对于正常肾样本过度表达的基因。使用在肾细胞癌中过度表达的这组基因对肾细胞癌组进行主成分分析，揭示了肾癌中存在2个主要亚组。使用由参与不同代谢途径的基因组成的不同基因集对肾细胞癌组进行一系列主成分分析，也揭示了肾细胞癌的相同2个主要亚组。使用相同基因进行艾森聚类也揭示了相同的2个主要肾细胞癌亚组。病理检查表明这2个亚组在病理分级上存在差异。鉴定出2个肾细胞癌亚组之间差异表达的基因。将每个肾细胞癌亚组和肾细胞癌样本库中的基因表达与17种不同正常组织中的基因表达进行比较，发现与这些正常组织相比，肾细胞癌中特异性过度表达的基因。作者得出结论，基因表达模式可能有助于进一步分类可能具有临床意义的肾细胞癌亚型。此外，与正常组织相比，在每组肾透明细胞癌中鉴定为过度表达的基因可能代表有用的治疗靶点。