To identify new target marker genes in renal cell carcinoma (RCC), we compared the gene expression profiles of clear cell RCC (cc-RCC) and normal kidney tissue using serial analysis of gene expression. Our results revealed that the transforming growth factor β induced 68 kDa protein (TGF-βI: β ig-h3 (BIGH3), plasminogen activator inhibitor-1 (PAI-1) and transforming growth factor β1 (TGF-β1) genes are up-regulated in cc-RCC. To further assess the role of BIGH3 in RCC, we investigated the mRNA expression levels of BIGH3, TGFβ1, PAI-1 and also of TGF-β1 related genes in 53 RCC and 30 normal kidney tissues by quantitative real-time RT-PCR (QRT-PCR). We further determined the BIGH3 protein levels in 52 cc-RCC paraffin-embedded tissue samples by immunohistochemistry. BIGH3 mRNA was found to be highly overexpressed in cc-RCC compared with normal tissues with an average ratio of 27. The mRNA levels of TGF-β1 and PAI-1 were also detected at significantly elevated levels in these cancers. Immunohistochemical analysis of BIGH3 also revealed strong staining in the majority of the cc-RCC samples. In addition, the up-regulation of BIGH3 and PAI-1 was found to correlate with the clinicopathological parameters associated with a poorer patient outcome, whereas TGF-β1 expression was determined to be unrelated to cancer progression. Strong BIGH3 staining thus tended to be associated with a poor prognosis. BIGH3 was also induced in some RCC cell lines by TGF-β1 stimulation and this correlated well with PAI-1 up-regulation, suggesting that these enhancements are regulated by a similar mechanism in these tumors.

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