The expression of high mobility group box 1 is associated with lymph node metastasis and poor prognosis in esophageal squamous cell carcinoma.

Abstract

The objective is to explore the expression of high mobility group box 1 (HMGB1) in esophageal squamous cell carcinoma (ESCC) and its relationship with lymph node metastasis and the prognosis of patients as well as possible mechanism. The expression of HMGB1, vascular endothelial growth factor C (VEGF-C) and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) in ESCC tissues, which were obtained from 72 patients who underwent radical esophagectomy, was detected through immunohistochemistry, firstly. The correlations between HMGB1 and VEGF-C, and micro-lymphatic vessel density (MLD), and lymph node metastasis, and the prognosis of patients, were analyzed by statistic analysis. The plasmid of small interference RNA (siRNA) targeting HMGB1, giving siHMGB1, was transfected into exponentially growing KYSE150 human esophageal squamous cancer cells and the expression of HMGB1 mRNA and protein was observed by Real-time PCR and Western Blot and the expression of VEGF-C was examined by ELISA. HMGB1 expressed highly in the nuclei and cytoplasm of carcinoma cells as well as the extracellular space in ESCC and was associated with lymph node metastasis, MLD, the expression of VEGF-C, TNM stage and the prognosis of patients (P < 0.05 or P < 0.01). In vitro, siHMGB1 inhibited the expression of HMGB1 mRNA and protein and the secretion of VEGF-C in KYSE150 cells. In ESCC, HMGB1 expresses highly and affects the prognosis of patients through regulating the expression of VEGF-C to promote lymphangiogenesis and lymph node metastasis, and HMGB1 might serve as the marker of progression and potential target for anti-lymphangiogenesis therapy.