Hsin-Chih Yeh1,2,3,4, Chun-Nung Huang3,4, Ching-Chia Li1,2,3,4, Lin-Li Chang1,5, Hui-Hui Lin3,4, Hung-Lung Ke1,3,4, A-Mei Huang6, Peir-In Liang7, Chien-Feng Li8,9,10, Wen-Jeng Wu11,12,13,14,15,16. 1. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 2. Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan. 3. Department of Urology, Kaohsiung Medical University Hospital, No.100, Tzyou 1st Road, Kaohsiung 807, Taiwan. 4. Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 5. Department of Microbiology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 6. Department of Biochemistry, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 7. Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 8. Department of Pathology, Chi Mei Medical Center, Chunghwa Road, Yung Kang District, Tainan 710, Taiwan. angelo.p@yahoo.com.tw. 9. Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan. angelo.p@yahoo.com.tw. 10. National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan. angelo.p@yahoo.com.tw. 11. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. wejewu@kmu.edu.tw. 12. Department of Urology, Kaohsiung Medical University Hospital, No.100, Tzyou 1st Road, Kaohsiung 807, Taiwan. wejewu@kmu.edu.tw. 13. Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. wejewu@kmu.edu.tw. 14. Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan. wejewu@kmu.edu.tw. 15. Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan. wejewu@kmu.edu.tw. 16. Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan. wejewu@kmu.edu.tw.
Abstract
PURPOSE: Bladder cancer (BC) is the most common malignancy in urinary system. The prognosis of metastatic BC is poor, but there remains no reliable marker to early detect metastasis. Dysregulated prenylated protein tyrosine phosphatases (PTPs) are commonly associated with cancer metastasis. From a published BC transcriptome, we identified that PTP IVA3 (PTP4A3) was the most significantly upregulated gene implicated in tumor progression among genes related to prenylated PTPs. We therefore analyzed PTP4A3 expression in our well-characterized cohort of BC. METHODS: By immunohistochemistry, PTP4A3 expression was determined using H-score. PTP4A3 expression of 295 BCs was compared with clinicopathological parameters, and the effect of PTP4A3 on cancer-specific survival (CSS) and metastasis-free survival (MFS) was also examined. Two independent sets of BCs were used to assess PTP4A3 protein and transcript expression in normal urothelium and different stage tumors. RESULTS: PTP4A3 overexpression was significantly associated with higher pT stage (P < 0.001), nodal metastasis (P < 0.001), vascular invasion (P < 0.001), and perineural invasion (P = 0.021). In multivariate analysis, PTP4A3 overexpression was an independent predictor for CSS (P < 0.001) and MFS (P = 0.007). Notably, the difference in CSS and MFS between high and low PTP4A3-expressing tumors was also significant in muscle-invasive BCs. PTP4A3 protein expression showed significant and stepwise increments from normal urothelium to noninvasive BC, invasive BC, and metastatic foci (P < 0.001). PTP4A3 transcript was also obviously upregulated in high-stage BC (P < 0.001). CONCLUSIONS: PTP4A3 may play a role in BC oncogenesis and is a predictive marker of metastasis. PTP4A3 overexpression represents an independent prognosticator for BC, suggesting its potential theranostic value.
PURPOSE:Bladder cancer (BC) is the most common malignancy in urinary system. The prognosis of metastatic BC is poor, but there remains no reliable marker to early detect metastasis. Dysregulated prenylated protein tyrosine phosphatases (PTPs) are commonly associated with cancer metastasis. From a published BC transcriptome, we identified that PTP IVA3 (PTP4A3) was the most significantly upregulated gene implicated in tumor progression among genes related to prenylated PTPs. We therefore analyzed PTP4A3 expression in our well-characterized cohort of BC. METHODS: By immunohistochemistry, PTP4A3 expression was determined using H-score. PTP4A3 expression of 295 BCs was compared with clinicopathological parameters, and the effect of PTP4A3 on cancer-specific survival (CSS) and metastasis-free survival (MFS) was also examined. Two independent sets of BCs were used to assess PTP4A3 protein and transcript expression in normal urothelium and different stage tumors. RESULTS:PTP4A3 overexpression was significantly associated with higher pT stage (P < 0.001), nodal metastasis (P < 0.001), vascular invasion (P < 0.001), and perineural invasion (P = 0.021). In multivariate analysis, PTP4A3 overexpression was an independent predictor for CSS (P < 0.001) and MFS (P = 0.007). Notably, the difference in CSS and MFS between high and low PTP4A3-expressing tumors was also significant in muscle-invasive BCs. PTP4A3 protein expression showed significant and stepwise increments from normal urothelium to noninvasive BC, invasive BC, and metastatic foci (P < 0.001). PTP4A3 transcript was also obviously upregulated in high-stage BC (P < 0.001). CONCLUSIONS:PTP4A3 may play a role in BC oncogenesis and is a predictive marker of metastasis. PTP4A3 overexpression represents an independent prognosticator for BC, suggesting its potential theranostic value.
Authors: Richard J Sylvester; Adrian P M van der Meijden; Willem Oosterlinck; J Alfred Witjes; Christian Bouffioux; Louis Denis; Donald W W Newling; Karlheinz Kurth Journal: Eur Urol Date: 2006-01-17 Impact factor: 20.096
Authors: John S Lazo; Elizabeth R Sharlow; Robert Cornelison; Duncan J Hart; Danielle C Llaneza; Anna J Mendelson; Ettore J Rastelli; Nikhil R Tasker; Charles N Landen; Peter Wipf Journal: Biomolecules Date: 2021-06-30