Prognostic value of UTX expression in patients with clear cell renal cell carcinoma.

PURPOSE: Our previous studies have identified an abnormal H3K27 methylation status in clear cell renal cell carcinoma (ccRCC). Ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) has been demonstrated as a histone demethylase that specifically targets di-methyl groups and tri-methyl groups on lysine 27 of histone H3 (H3K27me2/3). Herein, we explored the prognostic value of tumoral UTX expression in patient with ccRCC.

PATIENTS AND METHODS: We retrospectively enrolled 290 ccRCC patients underwent nephrectomy at a single institution between 2005 and 2007. UTX expression was assessed by immunohistochemistry on tissue microarrays and its prognostic value was assessed using Kaplan-Meier method and Cox proportional hazard model. Nomograms were generated as prediction models for overall survival (OS) and disease free survival (DFS).

RESULTS: Low expression of UTX was associated with reduced OS (P<0.001) and DFS (P = 0.001). In multivariate cox analyses, UTX was defined as an independent prognostic factor for OS (hazard ratio = 2.732 [95% CI: 1.650-4.493], P<0.001) and DFS (hazard ratio = 1.959 [95% CI: 1.153-3.326], P<0.001) as well. After stratifying patients into different risk groups using the Mayo Clinic stage, size, grade and necrosis/Leibovich score, decreased UTX expression was associated with shorter OS in both low-risk (P = 0.002) and high-risk groups (P = 0.030), but with shorter DFS only in low-risk group (P<0.001). Overall, 2 nomograms incorporating UTX expression with other parameters performed well in predicting patients' 5-year and 8-year OS and DFS (c-indices = 0.824 and 0.798, respectively).

CONCLUSIONS: UTX is a prognostic biomarker for patients with ccRCC both in OS and DFS prediction, especially significant in low-risk patients.