Sulfatase modifying factor 2 as a predictive biomarker for urothelial carcinoma.

Abstract

Sulfatases mediate the sulfation level of cell-surface heparan sulfates to regulate signal transduction, thereby promoting cancer progression. Sulfatase activation requires a sulfatase modifying factor (SUMF) for the modification of its catalytic domain. The role of the SUMF family in urothelial carcinoma (UC) has not been adequately evaluated. In this study, we used an online database and immunohistochemistry to assess genetic changes and the mRNA and protein expression of SUMFs and related candidate targets in UC. We found that SUMF1 and SUMF2 were amplified in UC tissues. High SUMF2 mRNA levels were associated with poor overall survival (OS) and disease-free survival (DFS) in bladder UC (BLCA) from The Cancer Genome Atlas (TCGA) dataset. High SUMF2 protein levels were associated with grade (P < 0.001), T status (P = 0.01), and stage (P = 0.006) in patients with BLCA. We also examined SUMF2 expression levels in upper tract UC (UTUC). SUMF2 expression was associated with stage (P = 0.046), poor OS (P = 0.0022), and DFS (P = 0.019) in patients with UTUC. Knockdown of SUMF2 significantly reduced the migration and invasion abilities of 5637 cells. Furthermore, SUMF2 mRNA levels negatively correlated with FBXW7 mRNA levels in BLCA. The SUMF2^high/FBXW7^low expression profile predicted the worst survival in BLCA. Taken together, SUMF2 expression is linked to unfavorable clinical outcomes in patients with UC and may serve as a useful prognostic biomarker for UC staging.