DPP4/CD26 overexpression in urothelial carcinoma confers an independent prognostic impact and correlates with intrinsic biological aggressiveness

Peir In Liang, Bi Wen Yeh, Wei Ming Li, Ti Chun Chan, I. Wei Chang, Chun Nung Huang, Ching Chia Li, Hung Lung Ke, Hsin Chih Yeh, Wen Jeng Wu, Chien Feng Li

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Urothelial carcinoma (UC) is common cancer worldwide. The molecular aberrations regarding tumor progression remain unclear. Pericellular proteolysis is crucial in tumorigenesis, but its significance is unexplored in UC. By data mining the datasets in Gene Expression Omnibus, specifically focus on the proteolysis pathway, and followed by a preliminary validation in a pilot batch of tumor samples, we identified that the upregulation of dipeptidyl peptidase 4 (DPP4) was most significantly associated with clinical aggressiveness of UCs. Quantitative RT-PCR confirmed upregulation of DPP4 mRNA in advanced stage UCs. The clinical significance of DPP4 expression was validated in our large cohort consists of 635 UCs from upper urinary tract and urinary bladder. Univariate and multivariate analyses show that DPP4 is an independent prognosticatory biomarker for disease-specific survival and metastasis-free survival. Comparing the DPP4 expression level of three urothelial cell lines with normal urothelial cells, J82 and RTCC-1 showed a significantly increased in transcript and protein expression. DPP4 knockdown as conducted by using short-hairpin RNA resulted in a significantly decreased cell viability, proliferation, migration, and invasion in J82 and RTCC-1 cells. These findings implicate that DPP4 plays a role in the aggressiveness of UCs, and can serve as a novel prognostic marker and therapeutic target.

Original languageEnglish
Pages (from-to)2995-3008
Number of pages14
JournalOncotarget
Volume8
Issue number2
DOIs
Publication statusPublished - Jan 1 2017
Externally publishedYes

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Keywords

  • DPP4
  • Overexpression
  • Proteolysis
  • Urothelial carcinoma

ASJC Scopus subject areas

  • Oncology

Cite this

Liang, P. I., Yeh, B. W., Li, W. M., Chan, T. C., Chang, I. W., Huang, C. N., Li, C. C., Ke, H. L., Yeh, H. C., Wu, W. J., & Li, C. F. (2017). DPP4/CD26 overexpression in urothelial carcinoma confers an independent prognostic impact and correlates with intrinsic biological aggressiveness. Oncotarget, 8(2), 2995-3008. https://doi.org/10.18632/oncotarget.13820