Abstract A110: Kinase gene expression profiles are associated with clinical outcomes in clear cell renal cell carcinoma patients

Abstract

Abstract A110 There are 516 known kinases in the human genome. These proteins are involved in regulating nearly all cellular processes through phosphorylation of target proteins. Because of their important role maintaining proper cellular function, they are often misregulated during tumorigenesis and associated with clinical outcomes in cancer patients. Similarly to other cancers, several kinases have been found to play key roles during development of renal cell carcinoma (RCC). However, less is known about the global expression status of these genes in RCC and their association with clinical outcomes. To identify variation in the RCC kinome, we performed a systematic analysis of gene expression for 503 human kinases using Illumina whole genome arrays in 93 tumor samples. Expression levels were analyzed with regard to associations with recurrence and overall survival. Six kinases were found to be significantly associated with an increased risk developing a recurrence, while two kinases were protective (p < 0.01). Furthermore, an expression signature comprised of these eight genes was able to identify low risk and high risk groups of patients (HR: 26.83, 95% CI: 3.77-190.78, p = 0.0010). These two risk groups also had significantly different recurrence-free survival times of 67.6 compared to 37.9 months (p = 0.0003) for the low and high risk groups, respectively. Expression of one of these eight genes, IKBKE, was also associated with a 5.3-fold increased risk of dying (95% CI: 1.93-14.59, p = 0.0012). Interestingly, this kinase was constantly associated with a poor prognosis in both univariable and multivariable analyses with similar HRs, indicating that expression levels of this gene may be a candidate, independent prognostic marker for RCC. IKBKE is a member of the NFκB signaling pathway and is responsible for regulation of NFκB-mediated transcriptional activation of genes involved in inflammation, immunity and stress responses. Overall, these results suggest a major role of global kinase gene expression in modulating clinical outcomes in RCC patients while identifying several candidate genes, including IKBKE, for further study. Citation Information: Cancer Prev Res 2008;1(7 Suppl):A110.