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

I. Wei Chang, Peir In Liang, Ching Chia Li, Wen Jeng Wu, Chun Nung Huang, Victor Chia Hsiang Lin, Chao Tien Hsu, Hong Lin He, Ting Feng Wu, Chih Hsin Hung, Chien Feng Li

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5441-5450
Number of pages10
JournalTumor Biology
Volume36
Issue number7
DOIs
Publication statusPublished - Jul 29 2015
Externally publishedYes

Keywords

  • HAS3
  • Hyaluronan synthase-3
  • Upper urinary tract
  • Urinary bladder
  • Urothelial carcinoma

ASJC Scopus subject areas

  • Cancer Research

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