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

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World Journal of Urology Aims and scope Submit manuscript

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.

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Acknowledgments

This study was supported by grants from Kaohsiung Medical University “Aim for the Top Universities (KMU-TP104E26, KMU-TP103G00, KMU-TP103G01, KMU-TP103G04, KMU-TP103G05)”, the health and welfare surcharge of tobacco products, Ministry of Health and Welfare (MOHW104-TDU-B-212-124-003), and Kaohsiung Municipal Ta-Tung Hospital (kmtth-102-014).

Authors’ contribution

HC Yeh contributed to data management, analyzed the data, and wrote and edited the manuscript. CN Huang contributed to data management and edited the manuscript. CC Li contributed to data collection and management. LL Chang edited the manuscript. HH Lin and HL Ke contributed to data management. AM Huang contributed to the project development. PI Liang involved in histopathological examination. CF Li involved in project development, data collection, data analysis, manuscript writing. WJ Wu contributed to data management and edited the manuscript.

Ethical standards

This research was approved by the Institute Review Board of the Chi Mei Medical Center (IRB10302015).

Author information

Authors and Affiliations

  1. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Hsin-Chih Yeh, Ching-Chia Li, Lin-Li Chang, Hung-Lung Ke & Wen-Jeng Wu

  2. Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan

    Hsin-Chih Yeh & Ching-Chia Li

  3. Department of Urology, Kaohsiung Medical University Hospital, No.100, Tzyou 1st Road, Kaohsiung 807, Taiwan

    Hsin-Chih Yeh, Chun-Nung Huang, Ching-Chia Li, Hui-Hui Lin, Hung-Lung Ke & Wen-Jeng Wu

  4. Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Hsin-Chih Yeh, Chun-Nung Huang, Ching-Chia Li, Hui-Hui Lin, Hung-Lung Ke & Wen-Jeng Wu

  5. Department of Microbiology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Lin-Li Chang

  6. Department of Biochemistry, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    A-Mei Huang

  7. Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Peir-In Liang

  8. Department of Pathology, Chi Mei Medical Center, Chunghwa Road, Yung Kang District, Tainan 710, Taiwan

    Chien-Feng Li

  9. Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan

    Chien-Feng Li

  10. National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan

    Chien-Feng Li

  11. Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan

    Wen-Jeng Wu

  12. Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan

    Wen-Jeng Wu

  13. Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan

    Wen-Jeng Wu

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  1. Hsin-Chih Yeh
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  2. Chun-Nung Huang
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  3. Ching-Chia Li
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  4. Lin-Li Chang
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  7. A-Mei Huang
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  9. Chien-Feng Li
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Correspondence to Chien-Feng Li or Wen-Jeng Wu.

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Yeh, HC., Huang, CN., Li, CC. et al. Overexpression of PTP4A3 is associated with metastasis and unfavorable prognosis in bladder cancer. World J Urol 34, 835–846 (2016). https://doi.org/10.1007/s00345-015-1698-x

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  • DOI: https://doi.org/10.1007/s00345-015-1698-x

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