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.
