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.
International journal of molecular sciences. 2019 Apr 03*** epublish ***
Hao-Lun Luo, Po-Huang Chiang, Chun-Chieh Huang, Yu-Li Su, Min-Tse Sung, Eing-Mei Tsai, Chang-Shen Lin, Po-Hui Chiang
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 83301, Taiwan. ., Institute of Population Health Sciences, National Health Research Institutes, Miaoli 35053, Taiwan. ., Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan. ., Department of Hematology and Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan. ., Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan. ., Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 83301, Taiwan. ., Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 83301, Taiwan. ., Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 83301, Taiwan. .