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Article

Methylation of SPARCL1 Is Associated with Oncologic Outcome of Advanced Upper Urinary Tract Urothelial Carcinoma

by
Hao-Lun Luo
1,2,
Po-Huang Chiang
3,4,5,
Chun-Chieh Huang
6,
Yu-Li Su
7,
Min-Tse Sung
8,
Eing-Mei Tsai
1,9,10,*,
Chang-Shen Lin
1,11 and
Po-Hui Chiang
1,2,*
1
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 83301, Taiwan
2
Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
3
Institute of Population Health Sciences, National Health Research Institutes, Miaoli 35053, Taiwan
4
Department of Health Risk Management, College of Management, China Medical University, Taichung 40402, Taiwan
5
Institute of Biomedical Informatics, National Yang Ming University, Taipei 11221, Taiwan
6
Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
7
Department of Hematology and Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
8
Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
9
Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 83301, Taiwan
10
Graduate Institute of Medicine, Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung 83301, Taiwan
11
Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 83301, Taiwan
 
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Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(7), 1653; https://doi.org/10.3390/ijms20071653
Submission received: 6 February 2019 / Revised: 27 March 2019 / Accepted: 28 March 2019 / Published: 3 April 2019
(This article belongs to the Special Issue Cancer Metabolism—Metabolites Regulation of Oncogenic Signaling and Epigenetics)
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Abstract

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 SPARCL1 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 (p = 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.
Keywords: SPARCL1; upper urinary tract urothelial carcinoma SPARCL1; upper urinary tract urothelial carcinoma

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MDPI and ACS Style

Luo, H.-L.; Chiang, P.-H.; Huang, C.-C.; Su, Y.-L.; Sung, M.-T.; Tsai, E.-M.; Lin, C.-S.; Chiang, P.-H. Methylation of SPARCL1 Is Associated with Oncologic Outcome of Advanced Upper Urinary Tract Urothelial Carcinoma. Int. J. Mol. Sci. 2019, 20, 1653. https://doi.org/10.3390/ijms20071653

AMA Style

Luo H-L, Chiang P-H, Huang C-C, Su Y-L, Sung M-T, Tsai E-M, Lin C-S, Chiang P-H. Methylation of SPARCL1 Is Associated with Oncologic Outcome of Advanced Upper Urinary Tract Urothelial Carcinoma. International Journal of Molecular Sciences. 2019; 20(7):1653. https://doi.org/10.3390/ijms20071653

Chicago/Turabian Style

Luo, Hao-Lun, Po-Huang Chiang, Chun-Chieh Huang, Yu-Li Su, Min-Tse Sung, Eing-Mei Tsai, Chang-Shen Lin, and Po-Hui Chiang. 2019. "Methylation of SPARCL1 Is Associated with Oncologic Outcome of Advanced Upper Urinary Tract Urothelial Carcinoma" International Journal of Molecular Sciences 20, no. 7: 1653. https://doi.org/10.3390/ijms20071653

APA Style

Luo, H.-L., Chiang, P.-H., Huang, C.-C., Su, Y.-L., Sung, M.-T., Tsai, E.-M., Lin, C.-S., & Chiang, P.-H. (2019). Methylation of SPARCL1 Is Associated with Oncologic Outcome of Advanced Upper Urinary Tract Urothelial Carcinoma. International Journal of Molecular Sciences, 20(7), 1653. https://doi.org/10.3390/ijms20071653

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