Oncotarget

Research Papers:

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 and Chien-Feng Li _

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Oncotarget. 2016; 7:78918-78931. https://doi.org/10.18632/oncotarget.12912

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Abstract

Meng-Chen Tsai1, Wei-Ming Li2,3,4,5, Chun-Nung Huang3,4, Hung-Lung Ke3,4, Ching-Chia Li3,4,6, Hsin-Chih Yeh3,4,6, Ti-Chun Chan1, Peir-In Liang7, Bi-Wen Yeh3,4, Wen-Jeng Wu2,3,4,6,8,9,10, Sher-Wei Lim11,12,13, Chien-Feng Li1,14,15,16,17

1 Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan

2 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

3 Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

4 Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

5 Department of Urology, Ministry of Health and Welfare Pingtung Hospital, Pingtung, Taiwan

6 Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan

7 Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

8 Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan

9 Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan

10 Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan

11Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan

12Department of Neurosurgery, Chi-Mei Medical Center, Chiali, Tainan, Taiwan

13Department of Nursing, Min-Hwei College of Health Care Management, Tainan, Taiwan

14Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan

15National Cancer Research Institute, National Health Research Institutes, Tainan, Taiwan

16Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

17Department of Internal Medicine and Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

Correspondence to:

Chien-Feng Li, email: angelo.p@yahoo.com.tw

Sher-Wei Lim, email: slsw0219@gmail.com

Keywords: urothelial carcinoma, transcriptome, DDR2, prognosis

Received: September 20, 2016     Accepted: October 19, 2016     Published: October 26, 2016

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 disease-specific 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.


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