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

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.

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).

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).

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