Gene Signatures of Progression and Metastasis in Renal Cell Cancer

Purpose: To address progression, metastasis and the clinical heterogeneity of Renal Cell Cancer (RCC).

Material and Methods: Transcriptional profiling with oligonucleotide microarrays (22,283 genes) was performed on 53 RCC tumors, 22 non-RCC renal tumors and 24 normal kidney samples. Samples were clustered based on gene expression profiles and specific gene sets for each renal tumor type were identified. Gene expression was correlated to disease progression and a metastasis gene signature was derived.

Results: Gene signatures were identified for each tumor type with 100% accuracy. Differentially expressed genes during early tumor formation and tumor progression to metastatic RCC were found. Subsets of these genes code for secreted proteins and membrane receptors and are both potential therapeutic or diagnostic targets. A gene pattern („metastatic signature“) derived from primary tumor was very accurate in classifying tumors with and without metastases at the time of surgery. A previously described „global“ metastatic signature derived by another group from various non-RCC tumors was validated in RCC.

Conclusion: Unlike previous studies, we describe highly accurate gene signatures for RCC subtypes and other renal tumors. Interestingly, the gene expression of primary tumors provides us information about the metastatic status in the respective patients and has the potential, if prospectively validated, to enrich the armamentarium of diagnostic tests in RCC. We validated in RCC, for the first time, a previously described metastatic signature and further demonstrated the feasibility of applying a gene signature across different microarray platforms. Transcriptional profiling allows a better appreciation of the molecular and clinical heterogeneity in RCC.