SULF2 is a novel diagnostic and prognostic marker for high-grade bladder cancer with lymphatic metastasis

BACKGROUND: Sulfatase 2 (SULF2) is a member of the sulfatase family, and its expression and clinical significance in bladder cancer (BCa) are not currently known. In this study, we attempted to evaluate SULF2 expression in BCa patients who underwent radical cystectomy (RC) and the relationship between SULF2 expression and clinical-pathological characteristics. METHODS: Data on SULF2 expression in BCa tissues was obtained from the Oncomine database and the Gene Expression Omnibus (GEO). The expression of SULF2 and vascular endothelial growth factor-D (VEGF-D) in BCa was evaluated by immunohistochemistry (IHC) in tissues from 203 patients who had undergone RC. We also explored the value of the measurement of SULF2 and VEGF-D expression for diagnosis and prognosis in BCa patients with lymphatic metastasis. RESULTS: We found an increase in SULF2 messenger RNA (mRNA) levels and gene amplification in BCa tissues from the Oncomine database. High expression of SULF2 was detected in 91/203 (44.8%) of BCa patients. Among these patients, 27 of 42 (64.3%) with lymphatic metastasis showed high SULF2 expression. Univariate analysis showed that tumor size, pathological stage, lymphatic metastasis, vascular infiltration, perineural infiltration, hydronephrosis, and VEGF-D and SULF2 expression were related to prognosis in BCa patients, and multivariable Cox regression analysis showed that SULF2 expression was an independent prognostic indicator. Receiver operating characteristic (ROC) analysis revealed that SULF2 expression resulted in an increased area under the curve (AUC) of 0.707, with a sensitivity of 71.4% and a specificity of 61.5%. CONCLUSIONS: The upregulation of SULF2 is associated with poor prognosis in high-grade BCa patients. It might be a novel diagnostic marker for BCa patients with lymphatic metastasis.