Original article
Differential gene expression identifies subgroups of renal cell carcinoma

https://doi.org/10.1016/j.lab.2006.04.001Get rights and content

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.

Section snippets

Tissue samples

Tissue from 16 ccRCC samples, 21 cases of normal kidney, and 518 samples from 16 different types of tissues, including 22 normal adipose tissue; 25 reparative bone samples from degenerative joint disease, 5 samples of normal bone, and 25 normal cervix; 41 normal colon; 22 normal liver; 36 normal lung; 20 normal skeletal muscle; 90 normal myometrium; 59 normal ovary; 12 normal skin; 28 normal small intestine; 7 normal stomach, 63 normal thymus; 59 tonsils with lymphoid hyperplasia; and 4 thyroid

Results

Quantification of gene expression using the Affymetrix GeneChip U_133 microarray set was performed on all samples. About 6800 of the ∼40,000 gene fragments examined were present in all 16 samples in the set of ccRCC. This number did not vary greatly if 6 or more samples of the set were included in the analysis (Fig 1, top panel). In an attempt to identify genes that are overexpressed in ccRCC compared with other tissues, a fold change analysis was performed comparing the set of ccRCC samples

Discussion

In this study, the authors examined the expression of ∼40,000 genes/ESTs in ccRCC and a variety of other tissues. The results confirmed and extended the findings of an earlier report23 with a larger number of ccRCC and normal tissue samples and the newer Affymetrix U_133 microarray set. Many genes were found to be differentially expressed in ccRCC compared with normal kidney. As the most promising potential targets of therapy would be expected to be overexpressed in ccRCC compared with not only

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