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Effects of HMGB1 on clinical prognosis of esophagus squamous cell carcinoma patients after chemoradiotherapy and the radiosensitivity of xenograft in nude mice
Zhang Xueyuan1, Yang Xingxiao2, Zou Naiyi1, Li Shuguang1, Shen Wenbin1, Zhu Shuchai1
1Department of Radiation Oncology, Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang 050011, China; 2Department of Infection Management, Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang 050011, China
AbstractObjective 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.
Zhang Xueyuan,Yang Xingxiao,Zou Naiyi et al. Effects of HMGB1 on clinical prognosis of esophagus squamous cell carcinoma patients after chemoradiotherapy and the radiosensitivity of xenograft in nude mice[J]. Chinese Journal of Radiation Oncology, 2023, 32(1): 48-54.
Zhang Xueyuan,Yang Xingxiao,Zou Naiyi et al. Effects of HMGB1 on clinical prognosis of esophagus squamous cell carcinoma patients after chemoradiotherapy and the radiosensitivity of xenograft in nude mice[J]. Chinese Journal of Radiation Oncology, 2023, 32(1): 48-54.
[1] Welsh J, Settle SH, Amini A, et al.Failure patterns in patients with esophageal cancer treated with definitive chemoradiation[J]. Cancer, 2012,118(10):2632-2640. DOI: 10.1002/cncr.26586.
[2] Ma H, Zheng S, Zhang X, et al.High mobility group box 1 promotes radioresistance in esophageal squamous cell carcinoma cell lines by modulating autophagy[J]. Cell Death Dis, 2019,10(2):136. DOI: 10.1038/s41419-019-1355-1.
[3] 焦健华, 焦点, 张景良, 等. HMGB1在膀胱尿路上皮癌中的表达及其对预后的意义[J].现代泌尿外科杂志,2021,26(1):21-25. DOI: 10.3969/j.issn.1009-8291.2021.01.005.
Jiao JH, Jiao D, Zhang JL, et al.The expression and prognostic value of HMGB1 in patients with urothelial carcinoma of the bladder[J]. Journal of Modern Urology, 2021,26(1):21-25. DOI: 10.3969/j.issn.1009-8291.2021.01.005.
[4] Gebhardt C, Riehl A, Durchdewald M, et al.RAGE signaling sustains inflammation and promotes tumor development[J]. J Exp Med, 2008,205(2):275-285. DOI: 10.1084/jem.20070679.
[5] Liu Z, Falo LD, You Z.Knockdown of HMGB1 in tumor cells attenuates their ability to induce regulatory T cells and uncovers naturally acquired CD8 T cell-dependent antitumor immunity[J]. J Immunol, 2011,187(1):118-125. DOI: 10.4049/jimmunol.1003378.
[6] van Beijnum JR, Nowak-Sliwinska P, van den Boezem E, et al. Tumor angiogenesis is enforced by autocrine regulation of high-mobility group box 1[J]. Oncogene, 2013,32(3):363-374. DOI: 10.1038/onc.2012.49.
[7] Tang D, Kang R, Livesey KM, et al.High-mobility group box 1 is essential for mitochondrial quality control[J]. Cell Metab, 2011,13(6):701-711. DOI: 10.1016/j.cmet.2011.04.008.
[8] Süren D, Yıldırım M, Demirpençe Ö, et al.The role of high mobility group box 1 (HMGB1) in colorectal cancer[J]. Med Sci Monit, 2014,20:530-537. DOI: 10.12659/MSM.890531.
[9] Wu D, Ding Y, Wang S, et al.Increased expression of high mobility group box 1 (HMGB1) is associated with progression and poor prognosis in human nasopharyngeal carcinoma[J]. J Pathol, 2008,216(2):167-175. DOI: 10.1002/path.2391.
[10] Wang X, Xiang L, Li H, et al. The role of HMGB1 signaling pathway in the development and progression of hepatocellular carcinoma: a review[J]. IntJ Mol Sci, 2015,16(9):22527-22540. DOI: 10.3390/ijms160922527.
[11] 杨兴肖, 张雪原, 邹乃祎, 等. RNA干扰HMGB1基因对食管鳞癌细胞X线照射后增殖与迁移能力影响[J].中华放射肿瘤学杂志,2019,28(12):933-938. DOI: 10.3760/cma.j.issn.1004-4221.2019.12.012.
Yang XX, Zhang XY, Zou NY, et al.Effect of HMGB1 knockdown by RNA interference on cell proliferation and migration of esophageal squamous cell carcinoma after X-ray radiation[J]. Chinese Journal of Radiation Oncology, 2019,28(12):933-938. DOI: 10.3760/cma.j.issn.1004-4221.2019.12.012.
[12] Zhang X, Yang X, Zhu S, et al.Radiosensitization of esophageal carcinoma cells by knockdown of HMGB1 expression[J]. Oncol Rep, 2019,41(3):1960-1970. DOI: 10.3892/or.2018.6923.
[13] Shrivastava S, Mansure JJ, Almajed W, et al.The role of HMGB1 in radioresistance of bladder cancer[J]. Mol Cancer Ther, 2016,15(3):471-479. DOI: 10.1158/1535-7163.MCT-15-0581.
2023, Vol. 32 
