Zhijie Xu1,2, Hemant Gujar2, Guanghou Fu1,2, Hamed Ahmadi2, Sumeet Bhanvadia2, Daniel J Weisenberger3, Baiye Jin1, Parkash S Gill4, Inderbir Gill2, Siamak Daneshmand2, Kimberly D Siegmund5, Gangning Liang2. 1. Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. 2. USC Institute of Urology and Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States. 3. Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States. 4. Division of Hematology in Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States. 5. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
Abstract
BACKGROUND: Muscle-invasive bladder cancer (MIBC) accounts for approximately 20% of all urothelial bladder carcinomas (UBC) at time of diagnosis, and up to 30% of patients with non-muscle invasive UBC will progress to MIBC over time. An increasing body of evidence has revealed a strong correlation between aberrant DNA methylation and tumorigenesis in MIBC. RESULTS: Using The Cancer Genome Atlas (TCGA) molecular data for 413 patients, we described a DNA methylation-based signature as a prognostic factor for overall survival (OS) in MIBC patients. By using a least absolute shrinkage and selection operator (LASSO) model, differentially methylated regions were first identified using multiple criteria followed by survival and LASSO analyses to identify DNA methylation probes related to OS and build a classifier to stratify patients with MIBC. The prognostic value of the classifier, referred to as risk score (RS), was validated in a held-out testing set from the TCGA MIBC cohort. Finally, receiver operating characteristic (ROC) analysis was used to compare the prognostic accuracy of the models built with RS alone, RS plus clinicopathologic features, and clinicopathologic features alone. We found that our seven-probe classifier-based RS stratifies patients into high- and low-risk groups for overall survival (OS) in the testing set (n = 137) (AUC at 3 years, 0.65; AUC at 5 years, 0.65). In addition, RS significantly improved the prognostic model when it was combined with clinical information including age, smoking status, Tumor (T) stage, and Lymph node metastasis (N) stage. CONCLUSIONS: The DNA methylation-based RS can be a useful tool to predict the accuracy of preoperative and/or post-cystectomy models of OS in MIBC patients.
BACKGROUND: Muscle-invasive bladder cancer (MIBC) accounts for approximately 20% of all urothelial bladder carcinomas (UBC) at time of diagnosis, and up to 30% of patients with non-muscle invasive UBC will progress to MIBC over time. An increasing body of evidence has revealed a strong correlation between aberrant DNA methylation and tumorigenesis in MIBC. RESULTS: Using The Cancer Genome Atlas (TCGA) molecular data for 413 patients, we described a DNA methylation-based signature as a prognostic factor for overall survival (OS) in MIBC patients. By using a least absolute shrinkage and selection operator (LASSO) model, differentially methylated regions were first identified using multiple criteria followed by survival and LASSO analyses to identify DNA methylation probes related to OS and build a classifier to stratify patients with MIBC. The prognostic value of the classifier, referred to as risk score (RS), was validated in a held-out testing set from the TCGA MIBC cohort. Finally, receiver operating characteristic (ROC) analysis was used to compare the prognostic accuracy of the models built with RS alone, RS plus clinicopathologic features, and clinicopathologic features alone. We found that our seven-probe classifier-based RS stratifies patients into high- and low-risk groups for overall survival (OS) in the testing set (n = 137) (AUC at 3 years, 0.65; AUC at 5 years, 0.65). In addition, RS significantly improved the prognostic model when it was combined with clinical information including age, smoking status, Tumor (T) stage, and Lymph node metastasis (N) stage. CONCLUSIONS: The DNA methylation-based RS can be a useful tool to predict the accuracy of preoperative and/or post-cystectomy models of OS in MIBC patients.
Authors: A Gordon Robertson; Jaegil Kim; Hikmat Al-Ahmadie; Joaquim Bellmunt; Guangwu Guo; Andrew D Cherniack; Toshinori Hinoue; Peter W Laird; Katherine A Hoadley; Rehan Akbani; Mauro A A Castro; Ewan A Gibb; Rupa S Kanchi; Dmitry A Gordenin; Sachet A Shukla; Francisco Sanchez-Vega; Donna E Hansel; Bogdan A Czerniak; Victor E Reuter; Xiaoping Su; Benilton de Sa Carvalho; Vinicius S Chagas; Karen L Mungall; Sara Sadeghi; Chandra Sekhar Pedamallu; Yiling Lu; Leszek J Klimczak; Jiexin Zhang; Caleb Choo; Akinyemi I Ojesina; Susan Bullman; Kristen M Leraas; Tara M Lichtenberg; Catherine J Wu; Nicholaus Schultz; Gad Getz; Matthew Meyerson; Gordon B Mills; David J McConkey; John N Weinstein; David J Kwiatkowski; Seth P Lerner Journal: Cell Date: 2018-08-09 Impact factor: 41.582
Authors: Marko Babjuk; Willem Oosterlinck; Richard Sylvester; Eero Kaasinen; Andreas Böhle; Juan Palou-Redorta; Morgan Rouprêt Journal: Eur Urol Date: 2011-03-22 Impact factor: 20.096