DPP4/CD26 overexpression in urothelial carcinoma confers an independent prognostic impact and correlates with intrinsic biological aggressiveness.
DPP4/CD26 overexpression in urothelial carcinoma confers an independent prognostic impact and correlates with intrinsic biological aggressiveness.
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DOI：
10.18632/oncotarget.13820
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发表时间：
2017-01-10
期刊：
影响因子：
--
通讯作者：
Li CF
中科院分区：
文献类型：
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作者：
Liang PI;Yeh BW;Li WM;Chan TC;Chang IW;Huang CN;Li CC;Ke HL;Yeh HC;Wu WJ;Li CF
尿路上皮癌（UC）是世界范围内常见的恶性肿瘤。关于肿瘤进展的分子畸变仍不清楚。细胞周蛋白水解在肿瘤发生中至关重要，但其在UC中的意义尚未探讨。通过对Gene Expression Omnibus中的数据集进行数据挖掘，特别关注蛋白水解途径，然后在中试批次的肿瘤样本中进行初步验证，我们确定二肽基肽酶4（DPP 4）的上调与UC的临床侵袭性最显著相关。定量RT-PCR证实了晚期UC中DPP 4 mRNA的上调。DPP 4表达的临床意义在我们的大型队列中得到验证，该队列由来自上尿路和膀胱的635个UC组成。单变量和多变量分析表明，DPP 4是疾病特异性生存和无转移生存的独立指示性生物标志物。与正常尿路上皮细胞相比，J82和RTCC-1细胞中DPP 4的转录和蛋白表达均显著增加。通过使用短发夹RNA进行的DPP 4敲低导致J82和RTCC-1细胞中的细胞活力、增殖、迁移和侵袭显著降低。这些发现暗示DPP 4在UC的侵袭性中起作用，并且可以作为新的预后标志物和治疗靶点。
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.