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Updated: May 25, 2026
Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays
Published on: October 23, 2019
Kinome expression profiling identifies IKBKE as a predictor of overall survival in clear cell renal cell carcinoma
Michelle A T Hildebrandt1, Weiqi Tan, Pheroze Tamboli
1Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. mhildebr@mdanderson.org
Abstract:
There are 516 known kinases in the human genome. Because of their important role maintaining proper cellular function, they are often misregulated during tumorigenesis and associated with clinical outcomes in cancer patients, including clear cell renal cell carcinoma (ccRCC). However, less is known about the global expression status of these genes in renal cell carcinoma and their association with clinical outcomes. We performed a systematic analysis of gene expression for 503 kinases in 93 tumor samples and adjacent normal tissues. Expression patterns for 41 kinases were able to clearly differentiate tumor and normal samples. Expression of I-kappa-B kinase epsilon (IKBKE) was associated with a 5.3-fold increased risk of dying [95% confidence interval (CI): 1.93-14.59, P-value: 0.0012]. Individuals with high IKBKE expression were at a significantly increased risk of death (hazard ratio: 3.34, 95% CI: 1.07-10.40, P-value: 0.038) resulting in a significantly reduced overall survival time compared with those with low IKBKE tumor expression (P-value: 0.049). These results for IKBKE were validated in a replication population consisting of 237 ccRCC patients (P-value: 0.0021). Furthermore, IKBKE was observed to be higher expressed in tumors compared with adjacent normal tissues (P-value < 10(-7)). IKBKE is a member of the nuclear factor-kappaB (NF-κB) signaling pathway and interestingly, gene expression patterns for other members of the NF-κB pathway were not associated with survival, suggesting that IKBKE gene expression may be an independent marker of variation in overall survival. Overall, these results support a novel role for IKBKE expression in modulating overall survival in ccRCC patients.
Insights
High expression of I-kappa-B kinase epsilon (IKBKE) in clear cell renal cell carcinoma (ccRCC) indicates a poorer prognosis. This kinase may serve as an independent marker for overall survival in ccRCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Kinases play crucial roles in cellular functions and are frequently dysregulated in cancer.
- Understanding kinase expression in renal cell carcinoma is vital for identifying prognostic markers.
- Clear cell renal cell carcinoma (ccRCC) is a significant clinical challenge.
Purpose of the Study:
- To systematically analyze the gene expression of kinases in ccRCC.
- To identify kinases associated with clinical outcomes in ccRCC patients.
- To investigate the prognostic value of IKBKE expression in ccRCC.
Main Methods:
- Genome-wide gene expression analysis of 503 kinases in 93 ccRCC tumor and normal tissue samples.
- Statistical analysis to identify kinases differentiating tumor from normal tissues.
- Validation of IKBKE expression and its association with survival in an independent cohort of 237 ccRCC patients.
Main Results:
- Expression patterns of 41 kinases significantly differentiated tumor from normal tissues.
- Elevated IKBKE expression was strongly associated with an increased risk of mortality (5.3-fold increased risk) and reduced overall survival in ccRCC patients.
- IKBKE expression was validated as an independent predictor of survival in ccRCC, with higher expression in tumors than normal tissues.
Conclusions:
- IKBKE gene expression is a novel and independent prognostic marker for overall survival in ccRCC.
- IKBKE's role in the nuclear factor-kappaB (NF-κB) pathway suggests specific therapeutic targets.
- Further research into IKBKE's function in ccRCC pathogenesis is warranted.
