Methylation of SPARCL1 Is Associated with Oncologic Outcome of Advanced Upper Urinary Tract Urothelial Carcinoma
Advanced upper urinary tract urothelial carcinoma (UTUC) is often associated with poor oncologic outcomes. The secreted protein acidic and rich in cysteine-like 1 (SPARCL1) protein, belongs to the SPARC-related family of matricellular proteins. Much literature has been published describing the role...
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2019-04-01
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| Series: | International Journal of Molecular Sciences |
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| author | Hao-Lun Luo Po-Huang Chiang Chun-Chieh Huang Yu-Li Su Min-Tse Sung Eing-Mei Tsai Chang-Shen Lin Po-Hui Chiang |
| author_facet | Hao-Lun Luo Po-Huang Chiang Chun-Chieh Huang Yu-Li Su Min-Tse Sung Eing-Mei Tsai Chang-Shen Lin Po-Hui Chiang |
| author_sort | Hao-Lun Luo |
| collection | DOAJ |
| description | Advanced upper urinary tract urothelial carcinoma (UTUC) is often associated with poor oncologic outcomes. The secreted protein acidic and rich in cysteine-like 1 (SPARCL1) protein, belongs to the SPARC-related family of matricellular proteins. Much literature has been published describing the role of SPARCL1 in the prognosis many cancers. In this study, methylated promoter regions in high-grade and high-stage upper urinary urothelial tumours compared with normal urothelium were analyzed and revealed that <i>SPARCL1</i> was the most significantly hypermethylated gene in UTUC tissues. Then we prospectively collected UTUC samples and adjacent normal urothelium for pyrosequencing validation, identifying significant CpG site methylation in UTUC tissues. In addition, SPARCL1 RNA levels were significantly lower in UTUC samples. Multivariate Cox regression analysis from 78 patients with solitary renal pelvic or ureteral pT3N0M0 urothelial carcinomas revealed that only negative SPARCL1 expression and nonpapillary tumour architecture were independently associated with systemic recurrence (<i>p</i> = 0.011 and 0.008, respectively). In vitro studies revealed that the behaviour of BFTC-909 cells was less aggressive and more sensitive to radiation or chemotherapy after SPARCL1 overexpression. Thus, SPARCL1 could be considered as a prognostic marker and help decision-making in clinical practice. |
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| spelling | doaj.art-5ede40d4f886499489b9ecb3c95006e22022-12-22T03:55:45ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-04-01207165310.3390/ijms20071653ijms20071653Methylation of SPARCL1 Is Associated with Oncologic Outcome of Advanced Upper Urinary Tract Urothelial CarcinomaHao-Lun Luo0Po-Huang Chiang1Chun-Chieh Huang2Yu-Li Su3Min-Tse Sung4Eing-Mei Tsai5Chang-Shen Lin6Po-Hui Chiang7Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 83301, TaiwanInstitute of Population Health Sciences, National Health Research Institutes, Miaoli 35053, TaiwanDepartment of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDepartment of Hematology and Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDepartment of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 83301, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 83301, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 83301, TaiwanAdvanced upper urinary tract urothelial carcinoma (UTUC) is often associated with poor oncologic outcomes. The secreted protein acidic and rich in cysteine-like 1 (SPARCL1) protein, belongs to the SPARC-related family of matricellular proteins. Much literature has been published describing the role of SPARCL1 in the prognosis many cancers. In this study, methylated promoter regions in high-grade and high-stage upper urinary urothelial tumours compared with normal urothelium were analyzed and revealed that <i>SPARCL1</i> was the most significantly hypermethylated gene in UTUC tissues. Then we prospectively collected UTUC samples and adjacent normal urothelium for pyrosequencing validation, identifying significant CpG site methylation in UTUC tissues. In addition, SPARCL1 RNA levels were significantly lower in UTUC samples. Multivariate Cox regression analysis from 78 patients with solitary renal pelvic or ureteral pT3N0M0 urothelial carcinomas revealed that only negative SPARCL1 expression and nonpapillary tumour architecture were independently associated with systemic recurrence (<i>p</i> = 0.011 and 0.008, respectively). In vitro studies revealed that the behaviour of BFTC-909 cells was less aggressive and more sensitive to radiation or chemotherapy after SPARCL1 overexpression. Thus, SPARCL1 could be considered as a prognostic marker and help decision-making in clinical practice.https://www.mdpi.com/1422-0067/20/7/1653SPARCL1upper urinary tract urothelial carcinoma |
| spellingShingle | Hao-Lun Luo Po-Huang Chiang Chun-Chieh Huang Yu-Li Su Min-Tse Sung Eing-Mei Tsai Chang-Shen Lin Po-Hui Chiang Methylation of SPARCL1 Is Associated with Oncologic Outcome of Advanced Upper Urinary Tract Urothelial Carcinoma International Journal of Molecular Sciences SPARCL1 upper urinary tract urothelial carcinoma |
| title | Methylation of SPARCL1 Is Associated with Oncologic Outcome of Advanced Upper Urinary Tract Urothelial Carcinoma |
| title_full | Methylation of SPARCL1 Is Associated with Oncologic Outcome of Advanced Upper Urinary Tract Urothelial Carcinoma |
| title_fullStr | Methylation of SPARCL1 Is Associated with Oncologic Outcome of Advanced Upper Urinary Tract Urothelial Carcinoma |
| title_full_unstemmed | Methylation of SPARCL1 Is Associated with Oncologic Outcome of Advanced Upper Urinary Tract Urothelial Carcinoma |
| title_short | Methylation of SPARCL1 Is Associated with Oncologic Outcome of Advanced Upper Urinary Tract Urothelial Carcinoma |
| title_sort | methylation of sparcl1 is associated with oncologic outcome of advanced upper urinary tract urothelial carcinoma |
| topic | SPARCL1 upper urinary tract urothelial carcinoma |
| url | https://www.mdpi.com/1422-0067/20/7/1653 |
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