title: Overexpression of PTP4A3 is associated with metastasis and unfavorable prognosis in bladder cancer.
abstract: OBJECTIVE
  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.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.|Department of Urology, Kaohsiung Medical University Hospital, No.100, Tzyou 1st Road, Kaohsiung 807, Taiwan.|Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Hsin-Chih
authors.initials: HC
authors.lastname: Yeh
authors.affiliation: Department of Urology, Kaohsiung Medical University Hospital, No.100, Tzyou 1st Road, Kaohsiung 807, Taiwan.|Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chun-Nung
authors.initials: CN
authors.lastname: Huang
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.|Department of Urology, Kaohsiung Medical University Hospital, No.100, Tzyou 1st Road, Kaohsiung 807, Taiwan.|Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ching-Chia
authors.initials: CC
authors.lastname: Li
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Microbiology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Lin-Li
authors.initials: LL
authors.lastname: Chang
authors.affiliation: Department of Urology, Kaohsiung Medical University Hospital, No.100, Tzyou 1st Road, Kaohsiung 807, Taiwan.|Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Hui-Hui
authors.initials: HH
authors.lastname: Lin
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Urology, Kaohsiung Medical University Hospital, No.100, Tzyou 1st Road, Kaohsiung 807, Taiwan.|Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Hung-Lung
authors.initials: HL
authors.lastname: Ke
authors.affiliation: Department of Biochemistry, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: A-Mei
authors.initials: AM
authors.lastname: Huang
authors.affiliation: Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Peir-In
authors.initials: PI
authors.lastname: Liang
authors.affiliation: Department of Pathology, Chi Mei Medical Center, Chunghwa Road, Yung Kang District, Tainan 710, Taiwan. angelo.p@yahoo.com.tw.|Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan. angelo.p@yahoo.com.tw.|National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan. angelo.p@yahoo.com.tw.
authors.forename: Chien-Feng
authors.initials: CF
authors.lastname: Li
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. wejewu@kmu.edu.tw.|Department of Urology, Kaohsiung Medical University Hospital, No.100, Tzyou 1st Road, Kaohsiung 807, Taiwan. wejewu@kmu.edu.tw.|Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. wejewu@kmu.edu.tw.|Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan. wejewu@kmu.edu.tw.|Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan. wejewu@kmu.edu.tw.|Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan. wejewu@kmu.edu.tw.
authors.forename: Wen-Jeng
authors.initials: WJ
authors.lastname: Wu
mesh_terms: D000368:Aged; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D011379:Prognosis; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology
chemical_list: D009363:Neoplasm Proteins; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases
keywords: Bladder cancer; Metastasis; PTP4A3; Prognosis