Department of Hepatobiliary Surgery, Navy General Hospital, PLA, Beijing, People's Republic of China.
302 Hospital of PLA, Beijing, People's Republic of China.
Onco Targets Ther. 2014 Feb 17;7:297-304. doi: 10.2147/OTT.S57355. eCollection 2014.
The aim of this study was to investigate the relationship between the expression of neutral endopeptidase (NEP) and dipeptidyl peptidase IV (DPP IV) proteins, and the clinical significance of the two proteins in patients with intrahepatic cholangiocarcinomas (IHCC).
Expression patterns and subcellular localizations of NEP and DPP IV proteins in 186 primary IHCC and 60 noncancerous liver tissue specimens were detected by immunohistochemistry.
Both the expression of NEP and DPP IV proteins in IHCC tissues were significantly higher than those in noncancerous liver tissues (both P<0.001). Of 186 patients with IHCC, 128 (68.82%) highly expressed both NEP and DPP IV proteins. In addition, the coexpression of NEP and DPP IV proteins was significantly associated with advanced tumor stage (P=0.009), positive lymph node metastasis (P=0.016) and distant metastasis (P=0.013), and the presence of recurrence (P=0.027). Moreover, Kaplan-Meier analysis showed that IHCC patients with high NEP expression, high DPP IV expression, and combined overexpression of NEP and DPP IV proteins all had poorer overall survival and early recurrence after surgery. Furthermore, Cox analysis suggested that NEP expression, DPP IV expression, and combined expression of NEP and DPP IV proteins were all independent prognostic markers for overall survival and recurrence-free survival in patients with IHCC.
Our data suggest, for the first time, that both the expression of NEP and DPP IV proteins may be upregulated in human IHCC tissues and the combined expression of NEP and DPP IV proteins may play important roles in progression and prognosis of patients with IHCC.
本研究旨在探讨中性内肽酶（NEP）和二肽基肽酶 IV（DPP IV）蛋白的表达与肝内胆管癌（IHCC）患者临床意义之间的关系。
采用免疫组织化学法检测 186 例原发性 IHCC 和 60 例非癌性肝组织标本中 NEP 和 DPP IV 蛋白的表达模式和亚细胞定位。
IHCC 组织中 NEP 和 DPP IV 蛋白的表达均明显高于非癌性肝组织（均 P<0.001）。186 例 IHCC 患者中，128 例（68.82%）NEP 和 DPP IV 蛋白高表达。此外，NEP 和 DPP IV 蛋白的共表达与肿瘤进展期（P=0.009）、淋巴结阳性转移（P=0.016）、远处转移（P=0.013）和复发（P=0.027）显著相关。此外，Kaplan-Meier 分析表明，NEP 表达高、DPP IV 表达高、NEP 和 DPP IV 蛋白联合过表达的 IHCC 患者术后总生存和早期复发均较差。进一步 Cox 分析表明，NEP 表达、DPP IV 表达和 NEP 和 DPP IV 蛋白联合表达均是 IHCC 患者总生存和无复发生存的独立预后标志物。
本研究首次提示，NEP 和 DPP IV 蛋白的表达均可能在人 IHCC 组织中上调，NEP 和 DPP IV 蛋白的联合表达可能在 IHCC 患者的进展和预后中发挥重要作用。
