title: Novel combination markers for predicting survival in patients with muscle invasive bladder cancer: USP18 and DGCR2.
abstract: We performed gene expression profiling in bladder cancer patients to identify cancer-specific survival-related genes in muscle invasive bladder cancer (MIBC) patients. Sixty-two patients with MIBC were selected as the original cohort and another 118 MIBC patients were chosen as a validation cohort. The expression of USP18, DGCR2, and ZNF699 genes were measured and we analyzed the association between gene signatures and survival. USP18 and DGCR2, were significantly correlated to cancer-specific death (P=0.020, P=0.007, respectively). Cancer-specific survival in the low USP18 or DGCR2 expression group was significantly longer than the high expression group (P=0.018, P=0.006, respectively). In multivariate Cox regression analysis, a combination of USP18 and DGCR2 mRNA expression levels were significant risk factors for cancer-specific death (HR, 2.106; CI, 1.043-4.254, P=0.038). Overall survival and cancer-specific survival rates in the low-combination group were significantly longer than those in the high-expression group (P=0.001, both). In conclusion, decreased expressions of USP18 and DGCR2 were significantly associated with longer cancer-specific survival, and also the combination of two genes was correlated to a longer survival for MIBC patients. Thus, the combination of USP18 and DGCR2 expression was shown to be a reliable prognostic marker for cancer-specific survival in MIBC.
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Korea.
authors.forename: Ye-Hwan
authors.identifier: 0000-0002-8676-7119
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Korea.
authors.forename: Won Tae
authors.identifier: 0000-0002-7482-4550
authors.initials: WT
authors.lastname: Kim
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Korea.
authors.forename: Pildu
authors.identifier: 0000-0002-5602-5376
authors.initials: P
authors.lastname: Jeong
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Korea. ; Section of Urological Oncology, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
authors.forename: Yun-Sok
authors.identifier: 0000-0003-3732-9814
authors.initials: YS
authors.lastname: Ha
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Korea.
authors.forename: Ho Won
authors.identifier: 0000-0002-8164-4427
authors.initials: HW
authors.lastname: Kang
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Korea.
authors.forename: Seok Joong
authors.identifier: 0000-0001-7737-4746
authors.initials: SJ
authors.lastname: Yun
authors.affiliation: Department of Food and Biotechnology, Chung-Ang University, Seoul, Korea.
authors.forename: Sung-Kwon
authors.identifier: 0000-0002-4514-3457
authors.initials: SK
authors.lastname: Moon
authors.affiliation: Department of Biomaterial Control, Dong-Eui University, Busan, Korea.
authors.forename: Yung Hyun
authors.identifier: 0000-0002-1454-3124
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Section of Urological Oncology, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
authors.forename: Isaac Yi
authors.identifier: 0000-0002-1967-5281
authors.initials: IY
authors.lastname: Kim
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Korea.
authors.forename: Wun-Jae
authors.identifier: 0000-0002-8060-8926
authors.initials: WJ
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D019042:Muscle Neoplasms / Q000556:secondary*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics / Q000378:metabolism*; D011237:Predictive Value of Tests; D012372:ROC Curve; D012044:Regression Analysis; D012307:Risk Factors; D043222:Ubiquitin Thiolesterase; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D019038:Platelet Glycoprotein GPIb-IX Complex; C515654:ZNF699 protein, human; C094990:adhesion receptor; D010450:Endopeptidases; C485560:USP18 protein, human; D043222:Ubiquitin Thiolesterase
keywords: DGCR2; Gene Expression Profiling; Survival; USP18 Protein, Human; Urinary Bladder Neoplasms