Gengyan Xiong, Jin Liu, Dong Fang, Qun He, Gang Wang, Zhisong He, Xuesong Li, Yinglu Guo, Liqun Zhou
Purpose: Epigenetic biomarkers and prognostic clinical factors in upper tract urothelial carcinoma (UTUC) are inconclusive. We conducted this study to identify gene promoter methylation status and predictors for UTUC patients.
Experimental design: We prospectively collected data for pathologically diagnosed UTUC patients who were treated with surgery in Peking University First Hospital (Beijing, China) from Aug 1, 1999 to Dec 31, 2011. Analysis for hypermethylation at ten CpG islands, which was performed for each DNA sample using bisulfite transformation and methylation-sensitive polymerase (MSP) chain reaction. The log-rank test and Cox regression were applied to identify prognostic factors, and two nomograms were utilized to construct the prognostic model for cancer specific survival (CSS) and bladder recurrence free survival (BRFS), respectively.
Results: Among the 687 patients analyzed, the median follow-up were 65 months (range, 3-144 months) for CSS and 49 months (range, 2-144 months) for BRFS. Two hundred and twenty-five (32.8%) patients died as a consequence of UTUC and 228 (33.2%) patients developed bladder recurrence (BR) during the follow-up period. Older age (P<0.001), male sex (P=0.033), tumor multifocality (P=0.008), ipsilateral hydronephrosis (P<0.001), larger main tumor diameter (>5 cm, P<0.001), higher tumor stage (P<0.001), positive N status (P=0.018), methylated TMEFF2 promoter (P=0.002) and unmethylated BRCA1 promoter (P=0.004) were significantly associated with poor CSS. Tumor multifocality (P=0.002), ureteroscopy history (P=0.001), lower tumor grade (P=0.046), unmethylated promoter of GDF15 (P=0.030) and RASSF1A (P=0.001) were considered as predictors to develop BR after surgery.
Conclusions: Methylation occurs commonly in UTUCs, may affect carcinogenic mechanisms, and is a well predictive factor for CSS and BRFS in UTUCs.
