title: Prognostic Value of Gene Methylation and Clinical Factors in Non-Muscle-Invasive Upper Tract Urothelial Carcinoma After Radical Nephroureterectomy.
abstract: To systematically analyze the outcomes and prognostic value of gene methylation and clinical parameters in non-muscle-invasive upper tract urothelial carcinoma (NMIUTUC) after radical nephroureterectomy (RNU).
  
  
  
  The methylation status of 10 selected genes and clinical parameters of 192 NMIUTUC patients who received RNU and postoperative intravesical mitomycin were assessed. Univariate and multivariate Cox regression models were performed to evaluate the prognostic factors of cancer-specific mortality and intravesical recurrence.
  
  
  
  For 192 NMIUTUC patients, 1-, 3-, and 5-year cancer-specific survival (CSS)/bladder recurrence-free survival (BRFS) rates were 98.4%/86.4%, 90.6%/74.6%, and 86.9%/62.4%, respectively. After the multivariate analysis, the methylation of ABCC6 (hazard ratio [HR], 3.46, P = .005), GDF15 (HR, 2.03, P = .002), multiple tumors (HR, 2.11, P = .049), impaired renal function (HR, 3.09, P = .004), and open RNU (HR, 2.14, P = .047) were independently associated with cancer-specific mortality, whereas the methylation of GDF15 (HR, 0.55, P = .022), RASSF1A (HR, 0.31, P = .006), multiple tumors (HR, 2.11, P = .002), and concomitant ipsilateral hydronephrosis (HR, 1.87, P = .022) were independently associated with intravesical recurrence after RNU. The c index of the multivariate model to predict cancer-specific mortality and intravesical recurrence was 0.81 and 0.78, respectively.
  
  
  
  As an early stage disease, NMIUTUC has better postoperative survival and later intravesical recurrence than upper tract urothelial carcinoma; however, the intravesical recurrence rate is not decreased. The nomogram can be used to accurately predict the oncologic outcomes of NMIUTUC patients and can be used to guide clinical decision making.
authors.affiliation: Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, National Urological Cancer Center, Beijing, China.
authors.forename: Yunchao
authors.initials: Y
authors.lastname: Xing
authors.affiliation: Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, National Urological Cancer Center, Beijing, China.
authors.forename: Gengyan
authors.initials: G
authors.lastname: Xiong
authors.affiliation: Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, National Urological Cancer Center, Beijing, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Fang
authors.affiliation: Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, National Urological Cancer Center, Beijing, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, National Urological Cancer Center, Beijing, China. Electronic address: pineneedle@sina.com.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, National Urological Cancer Center, Beijing, China. Electronic address: zhoulqmail@sina.com.
authors.forename: Liqun
authors.initials: L
authors.lastname: Zhou
mesh_terms: D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000601:surgery*; D019175:DNA Methylation; D005260:Female; D053263:Gene Regulatory Networks; D055436:Growth Differentiation Factor 15 / Q000235:genetics; D006801:Humans; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D015999:Multivariate Analysis; D009392:Nephrectomy / Q000379:methods*; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000601:surgery*
chemical_list: D055436:Growth Differentiation Factor 15; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D025521:Tumor Suppressor Proteins; C102029:ABCC6 protein, human; C526140:GDF15 protein, human; C411762:RASSF1 protein, human
keywords: Gene methylation; Nomogram; Non–muscle-invasive upper tract urothelial carcinoma; Prognostic factor; Radical nephroureterectomy