J Cancer 2022; 13(9):2717-2726. doi:10.7150/jca.73761 This issue

Research Paper

HMGB1 overexpression promotes a malignant phenotype and radioresistance in ESCC

Jing Dong1, Xueyuan Zhang1, Xingyu Du1, Naiyi Zou1, Wenbin Shen1, Ming Ma2, Yaojie Wang3, Shuchai Zhu1✉

1. Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, P. R. China
2. Department of Clinical Laboratory, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, P. R. China
3. Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, P. R. China

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Citation:
Dong J, Zhang X, Du X, Zou N, Shen W, Ma M, Wang Y, Zhu S. HMGB1 overexpression promotes a malignant phenotype and radioresistance in ESCC. J Cancer 2022; 13(9):2717-2726. doi:10.7150/jca.73761. Available from https://www.jcancer.org/v13p2717.htm

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Abstract

Graphic abstract

Esophageal cancer is a common malignant disease that is generally treated with radiotherapy. High mobility group box 1 (HMGB1) plays an essential role in tumor cell proliferation, migration, and cell cycle progression. Here, we aimed to clarify the effects of HMGB1 on radioresistance in esophageal squamous cell carcinoma (ESCC) cell lines and patient survival. We performed immunohistochemistry for HMGB1 in biopsy samples of 39 stage I-III ESCC patients grouped by HMGB1 expression status. Then, 1‐, 3‐, 5-, and 10‐year overall survival outcomes were calculated by Kaplan-Meier survival analysis. The cellular localization of HMGB1 was examined before and after irradiation by Immunofluorescence staining. Stable cell lines (KYSE30 and KYSE510) with differential HMGB1 expression were constructed using lentiviruses. Furthermore, we examined phosphorylated histone H2AX (γ-H2AX) expression in both HMGB1 overexpression and negative control groups by western blotting. HMGB1-negative expression was associated with superior ESCC patient 10-year survival (P=0.016). HMGB1 overexpression promoted cell migration, proliferation, and radioresistance and mitigated cell cycle arrest at the G0/G1 phase induced by irradiation. This demonstrates that HMGB1-positive expression is correlated with unfavorable clinical outcomes, and HMGB1 overexpression may promote the malignant phenotype of ESCC cells and induce radioresistance by regulating cell cycle distribution in ESCC.

Keywords: ESCC, HMGB1, malignant phenotype, radioresistance, γ-H2AX