High expression of brain-derived neurotrophic factor in intrahepatic cholangiocarcinoma is associated with intraneural invasion and unfavorable prognosis.

Objective: Brain-derived neurotrophic factor (BDNF) could promote the survival and differentiation of neural cells in peripheral and central nervous systems during development. Emerging evidences identified BDNF as an oncoprotein which could promotes progression and prognosis of tumors such as giloma, lung cancer and gastric cancer. We performed experiments to investigate the expression and clinical significance of BDNF in intrahepatic cholangiocarcinoma (IHCC).

Methods: The expression of BDNF and vascular endothelial growth factor (VEGF) was detected with immunohistochemistry in 96 patients with cholangiocarcinoma. The correlations between BDNF and the clinicopathologic factors were evaluated with Fisher test. The prognostic values of BDNF and VEGF were analyzed by the univariate analysis with Kaplan-Meier test and independent prognostic factor was identified by multivariate analysis with Cox-regression model. The effect of endogenous and exogenous BDNF on the invasion of IHCC cell line RBE was explored by transwell assay.

Results: The percentage of high expression of BDNF was 35.96% (34/96). High expression of BDNF was significantly associated with positive intraneural invasion (P=0.012) and low overall survival rate (P=0.006). High expression of BDNF was identified as an independent prognostic factor in IHCC (P=0.032). With Matrigel transwell assay, we demonstrated that both endogenous and exogenous BDNF could promote the invasion of IHCC cells.

Conclusions: High expression BDNF was identified as an independent risk in IHCC indicating poorer prognosis. Both endogenous and exogenous BDNF could promote the invasion of IHCC cells, indicating that BNDF may promote IHCC invasion in a paracrine or autocrine pathway.