Gene expression profiling of clear cell renal cell carcinoma: Gene identification and prognostic classification

To better understand the molecular mechanisms that underlie the tumorigenes is and progression of clear cell renal cell carcinoma (ccRCC), we studied t he gene expression profiles of 29 ccRCC tumors obtained from patients with diverse clinical outcomes by using 21,632 cDNA microarrays. We identified g ene expression alterations that were both common to most of the ccRCC studi ed and unique to clinical subsets. There was a significant distinction in g ene expression profile between patients with a relatively non-aggressive fo rm of the disease [100% survival after 5 years with the majority (15/17 or 88%) having no clinical evidence of metastasis] versus patients with a rela tively aggressive form of the disease (average survival time 25.4 months wi th a 0% 5-year survival rate). Approximately 40 genes most accurately make this distinction, some of which have previously been implicated in turnorig enesis and metastasis. To test the robustness and potential clinical useful ness of this molecular distinction, we simulated its use as a prognostic to ol in the clinical setting. In 96% of the ccRCC cases tested, the predictio n was compatible with the clinical outcome, exceeding the accuracy of predi ction by staging. These results suggest that two molecularly distinct forms of ccRCC exist and that the integration of expression profile data with cl inical parameters could serve to enhance the diagnosis and prognosis of ccR CC. Moreover, the identified genes provide insight into the molecular mecha nisms of aggressive ccRCC and suggest intervention strategies.