STAT3β Enhances Sensitivity to Concurrent Chemoradiotherapy by Inducing Cellular Necroptosis in Esophageal Squamous Cell Carcinoma.
STAT3β Enhances Sensitivity to Concurrent Chemoradiotherapy by Inducing Cellular Necroptosis in Esophageal Squamous Cell Carcinoma.
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STAT3β 通过诱导食管鳞状细胞癌中的细胞坏死性凋亡来增强对同步放化疗的敏感性。
DOI：
10.3390/cancers13040901
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发表时间：
2021-02-21
期刊：
影响因子：
5.2
通讯作者：
Xu LY
中科院分区：
文献类型：
--
作者：
Zheng ZY;Yang PL;Luo W;Yu SX;Xu HY;Huang Y;Li RY;Chen Y;Xu XE;Liao LD;Wang SH;Huang HC;Li EM;Xu LY
食管鳞状细胞癌（ESCC）患者的预后很差，5年生存率为15- 34%。我们采用免疫组织化学方法检测了105例接受同步放化疗（CCRT）的ESCC患者治疗前肿瘤活检组织中STAT 3 α和STAT 3 β的表达。数据显示，在细胞质中同时表现出高STAT 3 α表达和高STAT 3 β表达的ESCC患者具有显著更好的生存率。STAT 3 β高表达的ESCC患者对同步放化疗有完全反应。STAT 3 β过表达的ESCC细胞系表现出CCRT（铂加放射治疗）敏感性，导致细胞死亡。RNA测序结果显示，高表达STAT 3 β的食管鳞癌细胞在CCRT后发生坏死。总之，STAT 3 β可能用于预测CCRT的反应，这可能为ESCC的治疗提供重要的见解。同步化放疗（CCRT），尤其是铂类加放疗，被认为是晚期食管癌患者最有希望的治疗方式之一。STAT 3 β调节特异性靶基因，抑制肿瘤的发生和发展。它也是一个良好的预后标志物和对辅助放化疗（ACRT）反应的潜在标志物。本研究旨在探讨STAT 3 β与CCRT的关系。我们采用免疫组织化学方法检测了105例接受CCRT的ESCC患者治疗前肿瘤活检组织中STAT 3 α和STAT 3 β的表达。数据显示，在细胞质中同时表现出STAT 3 α高表达和STAT 3 β高表达的ESCC患者具有显著更好的生存率，并且STAT 3 β表达是独立的保护因素（HR = 0.424，p = 0.003）。同时，在65例接受铂类联合放射治疗的ESCC患者中，STAT 3 β高表达患者对CCRT表现出完全应答（p = 0.014）。在食管鳞癌细胞中，STAT 3 β高表达显著抑制集落形成和细胞增殖能力，提示STAT 3 β增强了对CCRT（铂加放射治疗）的敏感性。从机制上讲，通过RNA-seq分析，我们发现CCRT处理后高表达STAT 3 β细胞中TNF信号通路和坏死细胞死亡通路显著上调。总体而言，我们的研究强调STAT 3 β可能用于预测铂加放射治疗的反应，这可能为ESCC的治疗提供重要的见解。
The prognosis of esophageal squamous cell carcinoma (ESCC) patients is poor, with a five-year survival of 15–34%. We examined the expression of STAT3α and STAT3β in pretreatment tumor biopsies of 105 ESCC patients who received concurrent chemoradiotherapy (CCRT) by immunohistochemistry. The data showed that ESCC patients who demonstrate both high STAT3α expression and high STAT3β expression in the cytoplasm have a significantly better survival rate. Moreover, the ESCC patients with high STAT3β expression have a complete response to concurrent chemoradiotherapy. STAT3β-overexpressed ESCC cell lines exhibit CCRT (platinum plus radiation therapy) sensitivity, resulting in cell death. RNA sequencing found that ESCC cells highly expressing STAT3β undergo necrosis after CCRT. In summary, STAT3β could be potentially used to predict the response to CCRT, which may provide an important insight into the treatment of ESCC. Concurrent chemoradiotherapy (CCRT), especially platinum plus radiotherapy, is considered to be one of the most promising treatment modalities for patients with advanced esophageal cancer. STAT3β regulates specific target genes and inhibits the process of tumorigenesis and development. It is also a good prognostic marker and a potential marker for response to adjuvant chemoradiotherapy (ACRT). We aimed to investigate the relationship between STAT3β and CCRT. We examined the expression of STAT3α and STAT3β in pretreatment tumor biopsies of 105 ESCC patients who received CCRT by immunohistochemistry. The data showed that ESCC patients who demonstrate both high STAT3α expression and high STAT3β expression in the cytoplasm have a significantly better survival rate, and STAT3β expression is an independent protective factor (HR = 0.424, p = 0.003). Meanwhile, ESCC patients with high STAT3β expression demonstrated a complete response to CCRT in 65 patients who received platinum plus radiation therapy (p = 0.014). In ESCC cells, high STAT3β expression significantly inhibits the ability of colony formation and cell proliferation, suggesting that STAT3β enhances sensitivity to CCRT (platinum plus radiation therapy). Mechanistically, through RNA-seq analysis, we found that the TNF signaling pathway and necrotic cell death pathway were significantly upregulated in highly expressed STAT3β cells after CCRT treatment. Overall, our study highlights that STAT3β could potentially be used to predict the response to platinum plus radiation therapy, which may provide an important insight into the treatment of ESCC.
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