Overexpression of PTP4A3 is associated with metastasis and unfavorable prognosis in bladder cancer

Hsin Chih Yeh, Chun Nung Huang, Ching Chia Li, Lin Li Chang, Hui Hui Lin, Hung Lung Ke, A. Mei Huang, Peir In Liang, Chien Feng Li, Wen Jeng Wu

Research output: Contribution to journalArticle

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)835-846
Number of pages12
JournalWorld journal of urology
Volume34
Issue number6
DOIs
StatePublished - Jun 1 2016
Externally publishedYes

Keywords

  • Bladder cancer
  • Metastasis
  • PTP4A3
  • Prognosis

ASJC Scopus subject areas

  • Urology

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  • Cite this

    Yeh, H. C., Huang, C. N., Li, C. C., Chang, L. L., Lin, H. H., Ke, H. L., Huang, A. M., Liang, P. I., Li, C. F., & Wu, W. J. (2016). Overexpression of PTP4A3 is associated with metastasis and unfavorable prognosis in bladder cancer. World journal of urology, 34(6), 835-846. https://doi.org/10.1007/s00345-015-1698-x