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. 2014 Feb 17:7:297-304.
doi: 10.2147/OTT.S57355. eCollection 2014.

Prognostic significance of the combined expression of neutral endopeptidase and dipeptidyl peptidase IV in intrahepatic cholangiocarcinoma patients after surgery resection

Jianyong Zhu  1 , Xiaodong Guo  2 , Baoan Qiu  1 , Zhiyan Li  2 , Nianxin Xia  1 , Yingxiang Yang  1 , Peng Liu  1
Affiliations

Prognostic significance of the combined expression of neutral endopeptidase and dipeptidyl peptidase IV in intrahepatic cholangiocarcinoma patients after surgery resection

Jianyong Zhu et al. Onco Targets Ther. .

Abstract

Aim: 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).

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: clinicopathological characteristics; prognosis; tumor progression.

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Figures

Figure 1
Figure 1
Immunohistochemical staining for NEP and DPP IV in IHCC and noncancerous liver tissues. Notes: Original magnification ×200. (A and B) NEP and DPP IV strongly positive expression was found in cell membrane and cytoplasm at various levels in IHCC tissues. (C and D) NEP and DPP IV weakly positive expression was found in cell membrane and cytoplasm at various levels in IHCC tissues. (E and F) NEP and DPP IV negative expression in noncancerous liver tissues. Abbreviations: DPP IV, dipeptidyl peptidase IV; IHCC, intrahepatic cholangio‐carcinoma; NEP, neutral endopeptidase.
Figure 2
Figure 2
Overall survival and recurrence-free survival curves for two groups defined by low and high expression of NEP or DPP IV, and for four groups defined by combined expression of NEP and DPP IV, of patients with IHCC. Notes: Kaplan–Meier analysis showed 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. (A and B) low and high expression of NEP. (C and D) low and high expression DPP IV. (E and F) combined expression of NEP and DPP IV. Abbreviations: DPP IV, dipeptidyl peptidase IV; IHCC, intrahepatic cholangiocarcinoma; NEP, neutral endopeptidase.
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