DDR2 overexpression in urothelial carcinoma indicates an unfavorable prognosis: A large cohort study

Meng Chen Tsai, Wei Ming Li, Chun Nung Huang, Hung Lung Ke, Ching Chia Li, Hsin Chih Yeh, Ti Chun Chan, Peir In Liang, Bi Wen Yeh, Wen Jeng Wu, Sher Wei Lim, Chien Feng Li

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

The migration ability of urothelial carcinoma corresponding to dismal prognosis had not been fully investigated. The interaction of extracellular collagen with a unique transmembrane receptor tyrosine kinase, Discoidin domain receptor 2 (DDR2), was selected by data mining. We arranged real-time reverse transcription polymerase chain reaction assays to evaluate the transcript levels in 26 urinary tract urothelial carcinoma and 26 urinary bladder urothelial carcinoma specimens, showing significantly increase corresponding to advanced primary stage (p = 0.003 and p < 0.001, respectively). An immunohistochemistry analysis and H-score calculation were performed to determine DDR2 expression in 340 urinary tract urothelial carcinoma and 295 urinary bladder urothelial carcinoma. Assessments of the correlation to clinicopathologic features, disease-specific survival, and metastasis-free survival were conducted. The transcript levels in advanced stage were higher than those in early stage and were correlated with poor prognosis. The higher expression was positively correlated to higher pT status (p < 0.001), higher histological grade (urinary tract, p = 0.041; urinary bladder, p < 0.001), greater vascular invasion (p < 0.001), and higher mitotic rate (urinary tract, p = 0.039; urinary bladder, p < 0.001). Higher expression also indicates significantly worse diseasespecific survival and metastasis-free survival. In vitro study revealed knockdown of DDR2 resulted in a depletion of cellular viability, migratory, and invasive ability, supporting the oncogenic function of DDR2.

Original languageEnglish (US)
Pages (from-to)78918-78931
Number of pages14
JournalOncotarget
Volume7
Issue number48
DOIs
StatePublished - 2016
Externally publishedYes

Keywords

  • DDR2
  • Prognosis
  • Transcriptome
  • Urothelial carcinoma

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Tsai, M. C., Li, W. M., Huang, C. N., Ke, H. L., Li, C. C., Yeh, H. C., Chan, T. C., Liang, P. I., Yeh, B. W., Wu, W. J., Lim, S. W., & Li, C. F. (2016). DDR2 overexpression in urothelial carcinoma indicates an unfavorable prognosis: A large cohort study. Oncotarget, 7(48), 78918-78931. https://doi.org/10.18632/oncotarget.12912