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HAS3 underexpression as an indicator of poor prognosis in patients with urothelial carcinoma of the upper urinary tract and urinary bladder

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Tumor Biology

Abstract

Via data mining a published transcriptomic database of UBUC (GSE31684), we discovered hyaluronan synthase-3 (HAS3) as the most significant gene stepwise downregulated from early tumorigenesis to progression among those associated with hyaluronan synthase activity (GO:0050501). We consequently analyzed HAS3 protein expression and their association with clinicopathological factors and survival in our well-characterized cohort of urothelial carcinoma of upper urinary tract (UTUC) and urinary bladder (UBUC). HAS3 expression was assessed by immunohistochemistry and evaluated by using H score method in 295 UBUCs and 340 UTUCs, respectively. HAS3 protein expression statuses were further correlated with clinicopathological parameters and evaluated the prognostic significance for disease-specific survival (DSS) and metastasis-free survival (MeFS). HAS3 protein underexpression was significantly associated with advanced pT status, nodal metastasis, high histological grade, vascular invasion, and frequent mitoses in both groups of UCs. HAS3 underexpression not only predicted poorer DSS and MeFS with univariate analysis, but also indicated dismal DSS and MeFS in multivariate analysis. HAS3 underexpression is associated with advanced tumor stage and adverse pathological features, as well as implies inferior clinical outcomes for both groups of patients with UTUCs and UBUCs, suggesting its critical role in tumor progression in UCs and may serve as a prospective prognostic biomarker and a novel therapeutic target in UCs.

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Acknowledgments

This study is supported by Chi Mei Medical Center, Ministry of Health and Welfare (Health and Welfare surcharge of tobacco products, MOHW104-TDU-B-212-124-003), and Kaohsiung Medical University (KMU-TP103G01,KMU-TP103G00, KMU-TP103G04 & KMU-TP103G05).

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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, Chao-Tien Hsu & Hong-Lin He

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

    Peir-In Liang

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

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

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

    Ching-Chia Li

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

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

  7. Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

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

  8. Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    Wen-Jeng Wu

  9. Department of Urology, E-DA Hospital, Kaohsiung, Taiwan

    Victor Chia-Hsiang Lin

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

    Ting-Feng Wu & Chien-Feng Li

  11. Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan

    Chien-Feng Li

  12. National Cancer Research Institute, National Health Research Institutes, Tainan, Taiwan

    Chien-Feng Li

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

    Wen-Jeng Wu & Chien-Feng Li

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  1. I-Wei Chang
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  2. Peir-In Liang
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  3. Ching-Chia Li
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  6. Victor Chia-Hsiang Lin
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Correspondence to Chih-Hsin Hung or Chien-Feng Li.

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Chang, IW., Liang, PI., Li, CC. et al. HAS3 underexpression as an indicator of poor prognosis in patients with urothelial carcinoma of the upper urinary tract and urinary bladder. Tumor Biol. 36, 5441–5450 (2015). https://doi.org/10.1007/s13277-015-3210-z

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  • DOI: https://doi.org/10.1007/s13277-015-3210-z

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