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The Expression of High Mobility Group Box 1 is Associated with Lymph Node Metastasis and Poor Prognosis in Esophageal Squamous Cell Carcinoma

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Pathology & Oncology Research

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.

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Acknowledgments

We thank Guo Yuhong and Luo Ye for their technologic support. This work was supported by National Nature Science Foundation of China (Grant 81071981) and Tianjin Municipal Bureau of Public Health Science Foundation (Grant 09KZ82 &2010KZ68).

Funding

National Nature Science Foundation of China (Grant 81071981) and Tianjin Municipal Bureau of Public Health Science Foundation (Grant 09KZ82 & 2010KZ68)

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Authors and Affiliations

  1. Department of Esophageal Cancer, Key Laboratory of Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China

    Chen Chuangui, Tang Peng & Yu Zhentao

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  1. Chen Chuangui
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  2. Tang Peng
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  3. Yu Zhentao
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Correspondence to Yu Zhentao.

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Chuangui, C., Peng, T. & Zhentao, Y. The Expression of High Mobility Group Box 1 is Associated with Lymph Node Metastasis and Poor Prognosis in Esophageal Squamous Cell Carcinoma. Pathol. Oncol. Res. 18, 1021–1027 (2012). https://doi.org/10.1007/s12253-012-9539-3

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