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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• 作者：I-Wei Chang ; Peir-In Liang ; Ching-Chia Li ; Wen-Jeng Wu ; Chun-Nung Huang…
• 关键词：HAS3 ; Hyaluronan synthase ; 3 ; Urinary bladder ; Urothelial carcinoma ; Upper urinary tract
• 刊名：Tumor Biology
• 出版年：2015
• 出版时间：July 2015
• 年：2015
• 卷：36
• 期：7
• 页码：5441-5450
• 全文大小：857 KB
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• 作者单位：I-Wei Chang (1) (2)
  Peir-In Liang (3)
  Ching-Chia Li (4) (5) (6) (7)
  Wen-Jeng Wu (13) (4) (6) (7) (8)
  Chun-Nung Huang (4) (6) (7)
  Victor Chia-Hsiang Lin (1) (9)
  Chao-Tien Hsu (2)
  Hong-Lin He (2)
  Ting-Feng Wu (10)
  Chih-Hsin Hung (1)
  Chien-Feng Li (10) (11) (12) (13)
  
  1. Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan
  2. Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan
  3. Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
  4. Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
  5. Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
  6. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
  7. Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
  13. Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan
  8. Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
  9. Department of Urology, E-DA Hospital, Kaohsiung, Taiwan
  10. Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan
  11. Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan1111
  12. National Cancer Research Institute, National Health Research Institutes, Tainan, Taiwan
  
• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380

文摘

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.