Abstract
Microarray gene expression profiling has been used to distinguish histological subtypes of renal cell carcinoma (RCC), and consequently to identify specific tumor markers. The analytical procedures currently in use find sets of genes whose average differential expression across the two categories differ significantly. In general each of the markers thus identified does not distinguish tumor from normal with 100% accuracy, although the group as a whole might be able to do so. For the purpose of developing a widely used economically viable diagnostic signature, however, large groups of genes are not likely to be useful. Here we use two different methods, one a support vector machine variant, and the other an exhaustive search, to reanalyze data previously generated in our Lab (Lenburg et al. 2003). We identify 158 genes, each having an expression level that is higher (lower) in every tumor sample than in any normal sample, and each having a minimum differential expression across the two categories at a significance of 0.01. The set is highly enriched in cancer related genes (p = 1.6 × 10–12), containing 43 genes previously associated with either RCC or other types of cancer. Many of the biomarkers appear to be associated with the central alterations known to be required for cancer transformation. These include the oncogenes JAZF1, AXL, ABL2; tumor suppressors RASD1, PTPRO, TFAP2A, CDKN1C; and genes involved in proteolysis or cell-adhesion such as WASF2, and PAPPA.
Highlights
Renal-cell carcinoma (RCC) is the most common kidney neoplasm, comprising 3% of all adult malignancies (Jemal et al 2003)
The 5-year survival rate of metastatic RCC is less than 10%
Microarray gene expression profiling has been used by ourselves (Lenburg et al 2003) and others (Young et al 2001; Boer et al 2001; Gieseg et al 2002; Young et al 2003; Yamazaki et al 2003; Lenburg et al 2003; Higgins et al 2003; Takahashi et al 2003; Sultmann et al 2005; Jones et al 2005) to distinguish the various histological subtypes of RCC, and to identify novel tumor markers
Summary
Renal-cell carcinoma (RCC) is the most common kidney neoplasm, comprising 3% of all adult malignancies (Jemal et al 2003). The 5-year survival rate of metastatic RCC is less than 10%. RCC is one of the most therapyresistant carcinomas, responding very poorly or not at all to radiotherapy, hormonal therapy, and chemotherapy. All these facts emphasize the importance of developing early diagnostic markers. The general procedure identifies markers in accordance with average differential expression level (fold change) and/or some level of significance as measured by the t-test. Lenburg et al used a 3-fold difference in expression and a level of significance of 0.03
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