Necdin overexpression predicts poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder

I. Wei Chang, Yu Hui Wang, Wen Jeng Wu, Peir In Liang, Wei Ming Li, Bi Wen Yeh, Ting Feng Wu, Hong Lin He, Steven Kuan Hua Huang, Chien Feng Li

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background and Aims: Oncogenesis is a multistep process, resulting from the accumulations of multiple mutations. Of these mutations, self-sufficiency in growth signals, i.e., disruption of cell growth regulation, is the first episode. Nonetheless, the genes associated with cell growth dysregulation have seldom been systematically evaluated in either urothelial carcinomas of upper urinary tract (UTUC) or urothelial carcinomas of urinary baldder (UBUC). By data mining a published transcriptomic dataset of UBUCs (GSE31684), we identified the NDN gene as one of the most significant of those associated with the regulation of cell growth and found this gene is associated with advanced tumor status and metastatic disease (GO:0001558). Accordingly, we analyzed NDN transcript and protein expression with their clinicopathological significance. Materials and Methods: We used real time RT-PCR to detect NDN transcript levels in 27 UTUCs and 27 UBUCs, respectively. Immunohistochemical study was performed to determine NDN protein (a.k.a. Necdin) expression evaluated by H-score method in 340 UTUCs and 295 UBUCs. NDN expression was further correlated with clinicopathological features and disease-specific survival (DSS) and metastasis-free survival (MeFS). Results: NDN transcriptional level was significantly higher in UCs of both sites with stepwise more advanced pT statuses. Through immunohistochemistry, we found NDN protein expression was significantly associated with adverse clinicopathological parameters, e.g., advanced pT status, nodal metastasis, high grade histological patterns, and frequent mitotses (all P < 0.05). In univariate analysis, NDN overexpression not only predicted worse DSS and MeFS in both the UTUC and UBUC groups, it also served as an independent prognostic factor for DSS and MeFS in multivariate analysis (all P < 0.05). Conclusions: NDN may play an important role in tumor progression in UC and could serve as a prognostic biomarker and a potential novel therapeutic target in UC.

Original languageEnglish
Pages (from-to)304-313
Number of pages10
JournalJournal of Cancer
Volume7
Issue number3
DOIs
Publication statusPublished - Jan 1 2016
Externally publishedYes

Keywords

  • NDN gene
  • Necdin
  • Prognosis
  • Urothelial carcinoma

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Chang, I. W., Wang, Y. H., Wu, W. J., Liang, P. I., Li, W. M., Yeh, B. W., Wu, T. F., He, H. L., Huang, S. K. H., & Li, C. F. (2016). Necdin overexpression predicts poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder. Journal of Cancer, 7(3), 304-313. https://doi.org/10.7150/jca.13638