I-Wei Chang1, Victor Chia-Hsiang Lin2, Hong-Lin He3, Chao-Tien Hsu3, Ching-Chia Li4, Wen-Jeng Wu5, Chun-Nung Huang6, Ting-Feng Wu7, Chien-Feng Li8. 1. Institute of Biotechnology and Chemical Engineering, I-Shou University Kaohsiung, Taiwan ; Department of Pathology, E-DA Hospital/I-Shou University Kaohsiung, Taiwan. 2. Institute of Biotechnology and Chemical Engineering, I-Shou University Kaohsiung, Taiwan ; Department of Urology, E-DA Hospital/I-Shou University Kaohsiung, Taiwan. 3. Department of Pathology, E-DA Hospital/I-Shou University Kaohsiung, Taiwan. 4. Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung, Taiwan ; Department of Urology, Kaohsiung Municipal Ta-Tung Hospital Kaohsiung, Taiwan ; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University Kaohsiung, Taiwan ; Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University Kaohsiung, Taiwan. 5. Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung, Taiwan ; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University Kaohsiung, Taiwan ; Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University Kaohsiung, Taiwan ; Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University Kaohsiung, Taiwan. 6. Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung, Taiwan ; Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University Kaohsiung, Taiwan. 7. Department of Biotechnology, Southern Taiwan University of Science and Technology Tainan, Taiwan. 8. Department of Biotechnology, Southern Taiwan University of Science and Technology Tainan, Taiwan ; Department of Pathology, Chi-Mei Medical Center Tainan, Taiwan ; National Cancer Research Institute, National Health Research Institutes Tainan, Taiwan.
Abstract
AIMS: Urothelial carcinoma (UC) is the most common tumor involving upper urinary tract (UTUC) and urinary bladder (UBUC) whose molecular survival determinants remains obscured. By computerizing a public transcriptomic database of UBUCs (GSE32894), we identified cell division cycle associated 5 (CDCA5) as the most significantly upregulated gene among those associated with G1-S transition of the mitotic cell cycle (GO:0000082). We therefore analyzed the clinicoptaological significance of CDCA5 expression in our well-characterized UC cohort. METHODS AND RESULTS: Quantigene assay was used to detect CDCA5 transcript levels in 36 UTUCs and 30 UBUCs. We used immunohistochemistry evaluated by H-scores to determine CDCA5 protein expression in 295 UBUCs and 340 UTUCs, respectively. CDCA5 expression was further correlated with clinicopathological features and disease-specific survival (DSS) and metastasis-free survival (MeFS). For both groups of UCs, increments of CDCA5 transcript levels were associated with higher pT status, CDCA5 protein overexpression was also significantly associated with advanced pT status, nodal metastasis, high histological grade, vascular invasion, and frequent mitoses. CDCA5 overexpression was predictive for worse DSS and MeFS in univariate and multivariate analysis. CONCLUSIONS: CDCA5 overexpression is associated with advanced clinical features of UC, suggesting its potential value as a prognostic biomarker and a novel therapeutic target.
AIMS: Urothelial carcinoma (UC) is the most common tumor involving upper urinary tract (UTUC) and urinary bladder (UBUC) whose molecular survival determinants remains obscured. By computerizing a public transcriptomic database of UBUCs (GSE32894), we identified cell division cycle associated 5 (CDCA5) as the most significantly upregulated gene among those associated with G1-S transition of the mitotic cell cycle (GO:0000082). We therefore analyzed the clinicoptaological significance of CDCA5 expression in our well-characterized UC cohort. METHODS AND RESULTS: Quantigene assay was used to detect CDCA5 transcript levels in 36 UTUCs and 30 UBUCs. We used immunohistochemistry evaluated by H-scores to determine CDCA5 protein expression in 295 UBUCs and 340 UTUCs, respectively. CDCA5 expression was further correlated with clinicopathological features and disease-specific survival (DSS) and metastasis-free survival (MeFS). For both groups of UCs, increments of CDCA5 transcript levels were associated with higher pT status, CDCA5 protein overexpression was also significantly associated with advanced pT status, nodal metastasis, high histological grade, vascular invasion, and frequent mitoses. CDCA5 overexpression was predictive for worse DSS and MeFS in univariate and multivariate analysis. CONCLUSIONS:CDCA5 overexpression is associated with advanced clinical features of UC, suggesting its potential value as a prognostic biomarker and a novel therapeutic target.
Authors: Morgan Rouprêt; Marko Babjuk; Eva Compérat; Richard Zigeuner; Richard Sylvester; Max Burger; Nigel Cowan; Andreas Böhle; Bas W G Van Rhijn; Eero Kaasinen; Joan Palou; Shahrokh F Shariat Journal: Eur Urol Date: 2013-03-19 Impact factor: 20.096
Authors: James W F Catto; Abdel-Rahmene Azzouzi; Ishtiaq Rehman; Kenneth M Feeley; Simon S Cross; Najla Amira; Gaelle Fromont; Mathilde Sibony; Oliver Cussenot; Mark Meuth; Freddie C Hamdy Journal: J Clin Oncol Date: 2005-03-07 Impact factor: 44.544
Authors: Aurélie Mbeutcha; Morgan Rouprêt; Ashish M Kamat; Pierre I Karakiewicz; Nathan Lawrentschuk; Giacomo Novara; Jay D Raman; Christian Seitz; Evanguelos Xylinas; Shahrokh F Shariat Journal: World J Urol Date: 2016-04-21 Impact factor: 4.226
Authors: Aurélie Mbeutcha; Romain Mathieu; Morgan Rouprêt; Kilian M Gust; Alberto Briganti; Pierre I Karakiewicz; Shahrokh F Shariat Journal: Transl Androl Urol Date: 2016-10