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GPX2 underexpression indicates poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder

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Abstract

Purpose

Oxidative stress is believed to be one of the important etiologies in carcinogenesis that has not been systemically investigated in urothelial carcinoma (UC). Through data mining from a published transcriptomic database of UC of urinary bladders (UBUCs) (GSE31684), glutathione peroxidase 2 (GPX2) was identified as the most significant downregulated gene among those response to oxidative stress (GO:0006979). We therefore analyze GPX2 transcript and protein expressions and its clinicopathological significance.

Methods

Real-time RT-PCR assay was used to detect GPX2 mRNA level in 20 fresh UBUC specimens. Immunohistochemistry was used to determine GPX2 protein expression in 340 urothelial carcinomas of upper tracts (UTUCs) and 295 UBUCs with mean/median follow-up of 44.7/38.9 and 30.8/23.1 months, respectively. Its expression status was further correlated with clinicopathological features and evaluated for its impact on disease-specific survival and metastasis-free survival (MeFS).

Results

Decrease in GPX2 transcript level was associated with both higher pT and positive nodal status in 20 UBUCs (all p < 0.05). GPX2 protein underexpression was also significantly associated with advanced pT status, nodal metastasis, high histological grade, vascular invasion, and frequent mitoses in both groups of UCs (all p < 0.05). GPX2 underexpression not only predicted dismal DDS and MeFS at univariate analysis, but also implicated worse DDS (UTUC, p = 0.002; UBUC, p = 0.029) and MeFS (UTUC, p = 0.001; UBUC, p = 0.032) in multivariate analysis.

Conclusions

GPX2 underexpression is associated with advanced tumor status and implicated unfavorable clinical outcome of UCs, suggesting its role in tumor progression and may serve as a theranostic biomarker of UCs.

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Abbreviations

UC:

Urothelial carcinoma

UBUC:

Urinary bladder urothelial carcinoma

UTUC:

Upper urinary tract urothelial carcinoma

GEO:

Gene Expression Omnibus

GPX2:

Glutathione peroxidase 2

GPX:

Glutathione peroxidases

GSH:

Glutathione

DSS:

Disease-specific survival

MeFS:

Metastasis-free survival

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Acknowledgments

This work was supported by grants (EDAHP103051) from E-DA Hospital, Kaohsiung, Taiwan, and by Ministry of Health and Welfare (MOHW103-TD-B-111-05 and DOH102-TD-M-111-102001), as well as Chi Mei Medical Center (102-CM-TMU-01). The authors are grateful to the Biobank at Chi Mei Medical Center for providing tumor materials.

Conflict of interest

The authors have no potential conflict of interest.

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Author notes

    Authors and Affiliations

    1. Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan

      I-Wei Chang, Victor Chia-Hsiang Lin & Chih-Hsin Hung

    2. Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan

      I-Wei Chang

    3. Department of Urology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan

      Victor Chia-Hsiang Lin, Hua-Pin Wang & Yung-Yao Lin

    4. Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

      Wen-Jeng Wu, Chun-Nung Huang, Ching-Chia Li & Wei-Ming Li

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

      Wen-Jeng Wu, Chun-Nung Huang, Ching-Chia Li & Wei-Ming Li

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

      Wen-Jeng Wu

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

      Chun-Nung Huang, Ching-Chia Li, Wei-Ming Li & Chien-Feng Li

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

      Ching-Chia Li

    9. College of Medicine, Taipei Medical University, Taipei, Taiwan

      Jui-Yu Wu

    10. Department of Pathology, Chi Mei Foundation Medical Center, No. 901, Zhonghua Rd., Yongkang Dist., Tainan, 701, Taiwan

      Chien-Feng Li

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

      Chien-Feng Li

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

      Chien-Feng Li

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    1. I-Wei Chang
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    Correspondence to Chien-Feng Li.

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    Jui-Yu Wu and Chien-Feng Li have contributed equally as the senior authors of this article.

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    Chang, IW., Lin, V.CH., Hung, CH. et al. GPX2 underexpression indicates poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder. World J Urol 33, 1777–1789 (2015). https://doi.org/10.1007/s00345-015-1522-7

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    • DOI: https://doi.org/10.1007/s00345-015-1522-7

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