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

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 th...

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Autores principales: Liang, Peir-In, Yeh, Bi-Wen, Li, Wei-Ming, Chan, Ti-Chun, Chang, I-Wei, Huang, Chun-Nung, Li, Ching-Chia, Ke, Hung-Lung, Yeh, Hsin-Chih, Wu, Wen-Jeng, Li, Chien-Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356858/
https://www.ncbi.nlm.nih.gov/pubmed/27936466
http://dx.doi.org/10.18632/oncotarget.13820
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author Liang, Peir-In
Yeh, Bi-Wen
Li, Wei-Ming
Chan, Ti-Chun
Chang, I-Wei
Huang, Chun-Nung
Li, Ching-Chia
Ke, Hung-Lung
Yeh, Hsin-Chih
Wu, Wen-Jeng
Li, Chien-Feng
author_facet Liang, Peir-In
Yeh, Bi-Wen
Li, Wei-Ming
Chan, Ti-Chun
Chang, I-Wei
Huang, Chun-Nung
Li, Ching-Chia
Ke, Hung-Lung
Yeh, Hsin-Chih
Wu, Wen-Jeng
Li, Chien-Feng
author_sort Liang, Peir-In
collection PubMed
description 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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spelling pubmed-53568582017-04-20 DPP4/CD26 overexpression in urothelial carcinoma confers an independent prognostic impact and correlates with intrinsic biological aggressiveness Liang, Peir-In Yeh, Bi-Wen Li, Wei-Ming Chan, Ti-Chun Chang, I-Wei Huang, Chun-Nung Li, Ching-Chia Ke, Hung-Lung Yeh, Hsin-Chih Wu, Wen-Jeng Li, Chien-Feng Oncotarget Research Paper 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. Impact Journals LLC 2016-12-07 /pmc/articles/PMC5356858/ /pubmed/27936466 http://dx.doi.org/10.18632/oncotarget.13820 Text en Copyright: © 2017 Liang et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Liang, Peir-In
Yeh, Bi-Wen
Li, Wei-Ming
Chan, Ti-Chun
Chang, I-Wei
Huang, Chun-Nung
Li, Ching-Chia
Ke, Hung-Lung
Yeh, Hsin-Chih
Wu, Wen-Jeng
Li, Chien-Feng
DPP4/CD26 overexpression in urothelial carcinoma confers an independent prognostic impact and correlates with intrinsic biological aggressiveness
title DPP4/CD26 overexpression in urothelial carcinoma confers an independent prognostic impact and correlates with intrinsic biological aggressiveness
title_full DPP4/CD26 overexpression in urothelial carcinoma confers an independent prognostic impact and correlates with intrinsic biological aggressiveness
title_fullStr DPP4/CD26 overexpression in urothelial carcinoma confers an independent prognostic impact and correlates with intrinsic biological aggressiveness
title_full_unstemmed DPP4/CD26 overexpression in urothelial carcinoma confers an independent prognostic impact and correlates with intrinsic biological aggressiveness
title_short DPP4/CD26 overexpression in urothelial carcinoma confers an independent prognostic impact and correlates with intrinsic biological aggressiveness
title_sort dpp4/cd26 overexpression in urothelial carcinoma confers an independent prognostic impact and correlates with intrinsic biological aggressiveness
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356858/
https://www.ncbi.nlm.nih.gov/pubmed/27936466
http://dx.doi.org/10.18632/oncotarget.13820
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