Sulfatase-1 overexpression indicates poor prognosis in urothelial carcinoma of the urinary bladder and upper tract
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Hsiang-Ying Lee1,3,4,8, Bi-Wen Yeh3,4, Ti-Chun Chan5,6, Kei-Fu Yang2,3, Wei-Ming Li2,3,4,7, Chun-Nung Huang3,4, Hung-Lung Ke3,4, Ching-Chia Li3,4,8, Hsin-Chih Yeh2,3,4,7, Peir-In Liang9, Yow-Ling Shiue6, Wen-Jeng Wu2,3,4,8,10,11,12 and Chien-Feng Li5,9,11,13,14,15
1Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
2Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
3Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
4Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
5Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan
6Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
7Department of Urology, Ministry of Health and Welfare Pingtung Hospital, Pingtung, Taiwan
8Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
9Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
10Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
11Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan
12Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung, Taiwan
13Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan
14National Cancer Research Institute, National Health Research Institutes, Tainan, Taiwan
15Department of Internal Medicine and Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Chien-Feng Li, email: firstname.lastname@example.org
Wen-Jeng Wu, email: email@example.com
Keywords: urothelial carcinoma, transcriptome, SULF1, prognosis
Received: November 25, 2016 Accepted: April 17, 2017 Published: May 03, 2017
Urothelial carcinoma (UC), arising from the urothelium of the urinary tract, can occur in the upper (UTUC) and the urinary bladder (UBUC). A representative molecular aberration for UC characteristics and prognosis remains unclear. Data mining of Gene Expression Omnibus focusing on UBUC, we identified sulfatase-1 (SULF1) upregulation is associated with UC progression. SULF1 controls the sulfation status of heparan sulfate proteoglycans and plays a role in tumor growth and metastasis, while its role is unexplored in UC. To first elucidate the clinical significance of SULF1 transcript expression, real-time quantitative RT-PCR was performed in a pilot study of 24 UTUC and 24 UBUC fresh samples. We identified that increased SULF1 transcript abundance was associated with higher primary tumor (pT) status. By testing SULF1 immunoexpression in independent UTUC and UBUC cohorts consisted of 340 and 295 cases, respectively, high SULF1 expression was significantly associated with advanced pT and nodal status, higher histological grade and presence of vascular invasion in both UTUC and UBUC. In multivariate survival analyses, high SULF1 expression was independently associated with worse DSS (UTUC hazard ratio [HR] = 3.574, P < 0.001; UBUC HR = 2.523, P = 0.011) and MeFS (UTUC HR = 3.233, P < 0.001; UBUC HR = 1.851, P = 0.021). Furthermore, depletion of SULF1 expression by using RNA interference leaded to impaired cell proliferative, migratory, and invasive abilities in vitro. In addition, we further confirmed oncogenic role of SULF1 with gain-of function experiments. In conclusion, our findings implicate the oncogenic role of SULF1 expression in UC, suggesting SULF1 as a prognostic and therapeutic target of UC.
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