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.

Expression of MicroRNA-325-3p and its potential functions by targeting HMGB1 in non-small cell lung cancer

“…Existing studies suggest that HMGB1 may have an important role in tumor progression beyond cancer development. The relation of HMGB1 overexpression with lymph node metastasis presence and advanced stage in hepatocellular carcinoma, headneck, and esophagus squamous cell carcinoma, and cervix uteri was demonstrated [24][25][26]. All their findings supported the view that HMGB1 is an oncogene.…”

Clinical Significance of HMGB1 Expression in Human Gastric Cancer

“…Finally, a total expression score was given ranging from 0 to 12. Based on the analysis, HMGBI expression was categorized in advance into two groups: low-level HMGBI expression (score 0-3) and highlevel HMGBI expression (score [4][5][6][7][8][9][10][11][12] …”

“…The cDNAmicroarray analysis performed to compare gene expression profiles of the highly invasive and the low invasive subclones originating from ovarian cancer shows that high HMGB 1 expression is associated with poor clinicopathologic features (3). According to the cellular localization, HMGB 1, expressed in the nuclei andcytoplasm ofcancer cells aswell as the extracellular space, is correlated with lymph node metastases and prognosis in esophageal squamous cell carcinoma (4). HMGB 1 overexpression is significantly associated with tumor grade, stage, shorter disease-free survival and overall survival, representing an independent prognostic factor for patients with bladder cancer (5).…”

Effect of ulinastatin on the expression and distribution of high mobility group box 1 in human colon carcinoma cells in vitro

“…HMGB1 may act as a mediator of angiogenesis, increasing the expression of angiogenic growth factors, including vascular endothelial growth factor (21). HMGB1 has been observed to lead to endothelial cell migration and Effect of ulinastatin on the expression and distribution of high mobility group box 1 in human colon carcinoma cells in vitro sprouting in vitro (22), mediate the upregulation of vascular endothelial growth factor C and enhance lymphangiogenesis (23). Overexpression of HMGB1 suppresses the activity of caspase-9 and capsase-3, suggesting that it interferes with the apoptotic mechanism at the level of apoptosomal caspase-9 activation.…”