Effects of HMGB1 on clinical prognosis of esophagus squamous cell carcinoma patients after chemoradiotherapy and the radiosensitivity of xenograft in nude mice
10.3760/cma.j.cn113030-20210622-00235
- VernacularTitle:HMGB1对食管癌患者预后生存及裸鼠移植瘤放射敏感性的影响
- Author:
Xueyuan ZHANG
1
;
Xingxiao YANG
;
Naiyi ZOU
;
Shuguang LI
;
Wenbin SHEN
;
Shuchai ZHU
Author Information
1. 河北医科大学第四医院放疗科，石家庄 050011
- Keywords:
Esophageal squamous cell carcinoma;
HMGB1;
Nude mouse xenograft;
Radiosensitivity
- From:
Chinese Journal of Radiation Oncology
2023;32(1):48-54
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the effects of high mobility group protein box 1 (HMGB1) on clinical prognosis of esophagus squamous cell carcinoma (ESCC) patients treated with chemoradiotherapy and the radiosensitivity of xenograft in nude mice.Methods:A total of 90 endoscopic biopsy specimens were obtained from ESCC patients treated with chemoradiotherapy. The expression level of HMGB1 was determined by immunohistochemical staining. High expression level was defined when staining was observed on ≥50% of the tumor cells. All patients were divided into the high expression group ( n=48) and low expression group ( n=42), and their survival information was retrospectively analyzed. Cell transfection was performed with the plasmid carrying human HMGB1-shRNA to knockdown HMGB1 expression in ECA109 cells and xenograft mouse models were established. The tumor volume and mass were calculated after irradiation with a dose of 15 Gy. The cell apoptosis in xenograft tissues were detected. Survival analysis was performed using Kaplan-Meier method. Univariate prognostic analysis was conducted by log-rank test. Intergroup comparison was performed by analysis of variance (ANOVA). Results:The expression level of HMGB1 was significantly associated with gross tumor volume, longest diameter of tumor, T staging and distant metastasis ( χ2=9.663, 5.625, 4.068, 7.146, all P<0.05). In the low expression group, the overall survival (OS) ( χ2=4.826, P=0.028), progression-free survival (PFS) ( χ2=4.390, P=0.036) were longer compared with that in the high expression group. Further analysis of HMGB1-high expression patients showed that the radiation dose and the combination of chemoradiotherapy did not significantly affect the OS or PFS of ESCC patients. We observed that knockdown of HMGB1 slowed the growth rate of xenograft, decreased the tumor volume and increased the apoptosis rate after irradiation. Conclusions:ESCC patients with high expression level of HMGB1 obtain poor prognosis after chemoradiotherapy, which can be enhanced by increasing the sensitivity to radiotherapy and chemotherapy. HMGB1 knockdown can effectively increase the radiosensitivity of xenograft in ESCC nude mice.
