Expression of BDNF, TrkB, VEGF and CD105 is associated with pelvic lymph node metastasis and prognosis in IB2-stage squamous cell carcinoma.

Abstract

Brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), vascular endothelial growth factor (VEGF) and CD105 are highly expressed in several types of cancer. The present study aimed to determine whether BDNF, TrkB, VEGF and CD105 are associated with the prognosis and metastasis of patients with cervical squamous cell carcinoma (SCC) at the IB2 stage. A total of 79 patients with IB2-stage SCC were enrolled in the present study. The expression levels of BDNF, TrkB, VEGF and CD105 in IB2-stage cervical cancer tissue were detected by immunohistochemistry and their association with clinicopathological indexes or prognostic factors was statistically analyzed. Reverse transcription quantitative PCR was used to detect whether the expression of VEGF was affected in SiHa cells co-cultured with BDNF. In addition, BDNF-induced SiHa cell migration and invasion were examined. BDNF expression in the cervical cancer samples was significantly associated with positive lymphovascular space invasion (P<0.001) and pelvic lymph node metastasis (P<0.05). In addition, microvessel density was verified as an independent prognostic factor for overall survival (P<0.05). In vitro analysis indicated that BDNF significantly induced cellular migration and invasion of SiHa cells in a dose-dependent manner (P<0.001). BDNF induced the expression of VEGF in SiHa cells, which was inhibited by BDNF antibodies or an inhibitor of TrkB receptor (P<0.05). BDNF may be considered a useful indicator of pelvic metastasis, which is involved in the aggressive spread of IB2-stage SCC. BDNF-induced upregulation of VEGF was revealed to act as a pro-angiogenic factor in SCC (Trial registration no. http://apps.who.int/trialsearch/; ChiCTR1800017778).