Evidence-Based Medicine
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World J Gastroenterol. Apr 14, 2014; 20(14): 4076-4084
Published online Apr 14, 2014. doi: 10.3748/wjg.v20.i14.4076
Clinical significance of nerve growth factor and tropomyosin-receptor-kinase signaling pathway in intrahepatic cholangiocarcinoma
Xiao-Qing Yang, Yun-Fei Xu, Sen Guo, Yi Liu, Shang-Lei Ning, Xiao-Fei Lu, Hui Yang, Yu-Xin Chen
Xiao-Qing Yang, Yun-Fei Xu, Sen Guo, Yi Liu, Shang-Lei Ning, Hui Yang, Yu-Xin Chen, Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
Xiao-Qing Yang, Department of Pathology, Shandong University, Jinan 250012, Shandong Province, China
Xiao-Fei Lu, Department of Gastrointestinal Surgery, Central Hospital of Shandong University, Jinan 250012, Shandong Province, China
Author contributions: Yang XQ and Xu YF contributed equally to this work; Xu YF, Guo S, Liu Y, Ning SL, Lu XF, Yang H and Chen YX designed research; Yang XQ performed the IHC and follow-up; Xu YF performed the in vitro experiments; Xu YF and Yang XQ analyzed data; Xu YF and Chen YX wrote the paper.
Supported by National Natural Science Foundation of China, No. 81172044
Correspondence to: Yu-Xin Chen, Professor, Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, 44 Wenhuaxi Road, Jinan 250012, Shandong Province, China. cyxsdu2012@163.com
Telephone: +86-531-86907588 Fax: +86-0531-86907588
Received: December 17, 2013
Revised: February 25, 2014
Accepted: March 19, 2014
Published online: April 14, 2014
Processing time: 118 Days and 3 Hours
Abstract

AIM: To investigate the correlation between nerve growth factor-tropomyosin-receptor-kinase (NGF-TrkA) signaling pathway and prognosis in intrahepatic cholangiocarcinoma (IHCC).

METHODS: NGF and TrkA expression in 83 samples of IHCC was assessed by immunohistochemistry. Correlations between NGF-TrkA expression and clinicopathological features were analyzed by χ2 test. Moreover, we evaluated the association between NGF-TrkA and overall survival by univariate and multivariate analysis. With experiments in vitro, we investigated the crucial role of NGF-TrkA on proliferation and invasion of IHCC cells with recombinant NGF-β stimulation.

RESULTS: We found that NGF and TrkA expression was significantly related with differentiation (P = 0.024) and intraneural invasion (P = 0.003), respectively. Additionally, double higher expression of NGF and TrkA was identified as an independent prognostic factor in IHCC (P = 0.003). Moreover, we demonstrated that NGF-TrkA signaling pathway can promote IHCC proliferation and invasion.

CONCLUSION: NGF-TrkA double higher expression is an independent prognostic factor in IHCC. NGF-TrkA pathway can promote IHCC progression, indicating that NGF-TrkA may become a potential drug target.

Keywords: Nerve growth factor; Tropomyosin-receptor-kinase; Prognosis; Intrahepatic cholangiocarcinoma; Progression

Core tip: For the first time, we systemically investigated nerve growth factor (NGF) and tropomyosin-receptor-kinase (TrkA) expression in 83 intrahepatic cholangiocarcinoma(IHCC) samples by immunohistochemistry, and then analyzed the expression relationship with clinicopathological features, which resulted in finding that NGF and TrkA were significantly associated with differentiation (P = 0.024) and intraneural invasion (P = 0.003) respectively. Moreover, we found that NGF and TrkA double higher expression had poorer prognosis than others. NGF-TrkA double higher expression was further confirmed as an independent prognostic factor by multivariate analysis. With function assays we demonstrated that NGF-TrkA signaling pathway played a crucial role in cholangiocarcinoma proliferation and invasion, indicating NGF-TrkA pathway could be a promising potential drug target of intrahepatic cholangiocarcinoma.