Research Papers:

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 and Chien-Feng Li _

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Oncotarget. 2017; 8:2995-3008. https://doi.org/10.18632/oncotarget.13820

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Peir-In Liang1, Bi-Wen Yeh2,3, Wei-Ming Li2,3,4,5, Ti-Chun Chan6,7, I-Wei Chang8,9, Chun-Nung Huang2,3, Ching-Chia Li2,3,10, Hung-Lung Ke2,3, Hsin-Chih Yeh2,3,10, Wen-Jeng Wu2,3,4,10,11,12,13, Chien-Feng Li6,14,15,16,17

1Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

2Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

3Department of Urology, School of Medicine, College of Medicine, Kaohsiung, Medical University, Kaohsiung, Taiwan

4Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

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

6Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan

7Institute of Biomedical Science, National Sun Yat-sen University, Kaohsiung, Taiwan

8Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan

9School of Medicine for International Students, I-Shou University, Kaohsiung, Taiwan

10Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan

11Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan

12Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan

13Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan

14Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan

15Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan

16National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan

17Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

Correspondence to:

Chien-Feng Li, email: [email protected]

Wen-Jeng Wu, email: [email protected]

Keywords: urothelial carcinoma, DPP4, overexpression, proteolysis

Received: October 21, 2016     Accepted: November 30, 2016     Published: December 07, 2016


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.

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