Clinical significance of nerve growth factor and tropomyosin-receptor-kinase signaling pathway in intrahepatic cholangiocarcinoma

World J Gastroenterol. 2014 Apr 14;20(14):4076-84. doi: 10.3748/wjg.v20.i14.4076.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Bile Duct Neoplasms / metabolism*
  • Bile Ducts, Intrahepatic / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cholangiocarcinoma / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Nerve Growth Factor / metabolism*
  • Prognosis
  • Receptor, trkA / metabolism*
  • Signal Transduction
  • Treatment Outcome

Substances

  • NGF protein, human
  • Nerve Growth Factor
  • Receptor, trkA