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 uroth...
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| Format: | Article |
| Language: | English |
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Springer
2025-02-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-01859-y |
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| author | Wei-Ting Kuo Yi-Chen Lee Jia-Bin Liao Ching-Jiunn Tseng Yi-Fang Yang |
| author_facet | Wei-Ting Kuo Yi-Chen Lee Jia-Bin Liao Ching-Jiunn Tseng Yi-Fang Yang |
| author_sort | Wei-Ting Kuo |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-6525948059c0488bb5368843640cbc1e |
| institution | Kabale University |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-6525948059c0488bb5368843640cbc1e2025-02-09T12:43:22ZengSpringerDiscover Oncology2730-60112025-02-0116111210.1007/s12672-025-01859-ySulfatase modifying factor 2 as a predictive biomarker for urothelial carcinomaWei-Ting Kuo0Yi-Chen Lee1Jia-Bin Liao2Ching-Jiunn Tseng3Yi-Fang Yang4Division of Urology, Department of Surgery, Kaohsiung Veterans General HospitalDepartment of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical UniversityDepartment of Pathology and Laboratory Medicine, Kaohsiung Veterans General HospitalInstitute of Clinical Medicine, National Yang Ming Chiao Tung UniversityDepartment of Medical Education and Research, Kaohsiung Veterans General HospitalAbstract 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.https://doi.org/10.1007/s12672-025-01859-ySulfatasesSUMF2FBXW7Urothelial carcinoma |
| spellingShingle | Wei-Ting Kuo Yi-Chen Lee Jia-Bin Liao Ching-Jiunn Tseng Yi-Fang Yang Sulfatase modifying factor 2 as a predictive biomarker for urothelial carcinoma Discover Oncology Sulfatases SUMF2 FBXW7 Urothelial carcinoma |
| title | Sulfatase modifying factor 2 as a predictive biomarker for urothelial carcinoma |
| title_full | Sulfatase modifying factor 2 as a predictive biomarker for urothelial carcinoma |
| title_fullStr | Sulfatase modifying factor 2 as a predictive biomarker for urothelial carcinoma |
| title_full_unstemmed | Sulfatase modifying factor 2 as a predictive biomarker for urothelial carcinoma |
| title_short | Sulfatase modifying factor 2 as a predictive biomarker for urothelial carcinoma |
| title_sort | sulfatase modifying factor 2 as a predictive biomarker for urothelial carcinoma |
| topic | Sulfatases SUMF2 FBXW7 Urothelial carcinoma |
| url | https://doi.org/10.1007/s12672-025-01859-y |
| work_keys_str_mv | AT weitingkuo sulfatasemodifyingfactor2asapredictivebiomarkerforurothelialcarcinoma AT yichenlee sulfatasemodifyingfactor2asapredictivebiomarkerforurothelialcarcinoma AT jiabinliao sulfatasemodifyingfactor2asapredictivebiomarkerforurothelialcarcinoma AT chingjiunntseng sulfatasemodifyingfactor2asapredictivebiomarkerforurothelialcarcinoma AT yifangyang sulfatasemodifyingfactor2asapredictivebiomarkerforurothelialcarcinoma |