Abstract
Resistance to radiotherapy results in relapse and treatment failure in locally advanced esophageal squamous cell carcinoma (ESCC). High mobility group box 1 (HMGB1) is reported to be associated with the radioresistance in bladder and breast cancer. However, the role of HMGB1 in the radiotherapy response in ESCC has not been fully elucidated. Here, we investigated the role of HMGB1 to radioresistance in ESCC clinical samples and cell lines. We found that HMGB1 expression was associated with tumor recurrence after postoperative radiotherapy in locally advanced ESCC patients. HMGB1 knockdown in ESCC cells resulted in increased radiosensitivity both in vitro and in vivo. Autophagy level was found depressed in HMGB1 inhibition cells and activation of autophagy brought back cell’s radioresistance. Our results demonstrate that HMGB1 activate autophagy and consequently promote radioresistance. HMGB1 may be used as a predictor of poor response to radiotherapy in ESCC patients. Our finding also highlights the importance of the utility of HMGB1 in ESCC radiosensitization.
Highlights
Esophageal cancer is the ninth most common malignancy and ranks sixth in cancer deaths worldwide in 20131
We examined the association of tumor High mobility group box 1 (HMGB1) expression with in-field recurrence after postoperative radiotherapy (PORT) which may reflect tumor radioresistance
These results suggest that HMGB1 expression is clinically relevant to the in-field recurrence of locally advanced resected Esophageal squamous cell carcinoma (ESCC)
Summary
Esophageal cancer is the ninth most common malignancy and ranks sixth in cancer deaths worldwide in 20131. Esophageal squamous cell carcinoma (ESCC) is the major histological subtype of esophageal cancer in China[2]. The 5-year overall survival rate of ESCC is 15–25%. For the patients diagnosed at the locally advanced stage, the prognosis is even worse[3]. Preoperative chemoradiotherapy followed by esophagectomy has become the preferred approach for locally advanced esophageal cancer based according to the NCCN guidelines.
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