星博凡, 王宇, 刘超, 周倩倩, 张睿哲, 徐芳泉, 任玉, 周旋. 磷酸化EZH2在头颈部鳞癌中的表达特征及对化疗敏感性的影响[J]. 中国肿瘤临床, 2023, 50(21): 1086-1092. DOI: 10.12354/j.issn.1000-8179.2023.20230667
引用本文: 星博凡, 王宇, 刘超, 周倩倩, 张睿哲, 徐芳泉, 任玉, 周旋. 磷酸化EZH2在头颈部鳞癌中的表达特征及对化疗敏感性的影响[J]. 中国肿瘤临床, 2023, 50(21): 1086-1092. DOI: 10.12354/j.issn.1000-8179.2023.20230667
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Bofan Xing, Yu Wang, Chao Liu, Qianqian Zhou, Ruizhe Zhang, Fangquan Xu, Yu Ren, Xuan Zhou. Expression characteristics of phosphorylated EZH2 in head and neck squamous cell carcinoma and their effect on chemotherapy sensitivity[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2023, 50(21): 1086-1092. DOI: 10.12354/j.issn.1000-8179.2023.20230667
Citation: Bofan Xing, Yu Wang, Chao Liu, Qianqian Zhou, Ruizhe Zhang, Fangquan Xu, Yu Ren, Xuan Zhou. Expression characteristics of phosphorylated EZH2 in head and neck squamous cell carcinoma and their effect on chemotherapy sensitivity[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2023, 50(21): 1086-1092. DOI: 10.12354/j.issn.1000-8179.2023.20230667
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磷酸化EZH2在头颈部鳞癌中的表达特征及对化疗敏感性的影响

Expression characteristics of phosphorylated EZH2 in head and neck squamous cell carcinoma and their effect on chemotherapy sensitivity

    摘要
  • 摘要:
      目的  探究头颈部鳞状细胞癌（head and neck squamous cell carcinoma，HNSCC）中磷酸化Zeste同源增强子（enhancer of Zeste homolog 2，EZH2）的表达特征及对化疗敏感性的影响。
      方法  选取2018年1月至2021年3月天津医科大学肿瘤医院HNSCC患者组织标本及临床资料53例。免疫组织化学染色分析HNSCC组织标本中p-EZH2S21、p-STAT3Y705、HIF-1α和Ki-67的表达水平。Western blot检测HNSCC组织和细胞株中p-EZH2S21的表达情况。在HNSCC细胞中构建EZH2野生型（EZH2-WT）和EZH2 S21位点突变（EZH2-S21A）的稳转细胞，CCK8实验和平板克隆实验检测EZH2以及S21位点磷酸化对HNSCC细胞增殖能力及其对顺铂（cisplatin，DDP）和5-氟尿嘧啶（5-fluorouracil，5-FU）敏感性的影响。
      结果  HNSCC中p-EZH2S21表达升高，并且与p-STAT3Y705（P<0.05），HIF-1α（P<0.01）表达呈正相关。临床特征相关性分析发现HNSCC中p-EZH2S21表达与淋巴结转移（P<0.000 5）、T分期（P<0.05）、N分期（P<0.000 1）和AJCC分期（P<0.05）呈正相关。体外实验证实EZH2表达促进 HNSCC细胞增殖能力并且抑制其对化疗的敏感性，抑制EZH2 S21磷酸化可以恢复肿瘤细胞对DDP和5-FU的敏感性。
      结论  p-EZH2S21在HNSCC肿瘤进展中具有重要作用，S21位点磷酸化是EZH2影响 HNSCC细胞增殖及其对化疗敏感性的重要途径。

     

    Abstract:
      Objective  To investigate the expression characteristics of phosphorylated enhancer of Zeste homolog 2 (EZH2) in head and neck squamous cell carcinoma (HNSCC) and their effect on chemosensitivity.
      Methods  Fifty-three patients with HNSCC treated between January 2018 and March 2021 in Tianjin Medical University Cancer Institute & Hospital were selected. Expression levels of p-EZH2S21, p-STAT3Y705, HIF-1α, and Ki-67 in HNSCC tissues were analyzed by immunohistochemical staining. Western blot was used to detect p-EZH2S21 expression in HNSCC tissues and cell lines. HNSCC cell lines stably transfected with wild type (EZH2-WT) or S21 mutant EZH2 (EZH2-S21A) were constructed. CCK8 and colony formation assays were performed to detect the effect of EZH2 and S21 phosphorylation on HNSCC cell proliferation and their sensitivity to cisplatin (DDP) and 5-fluorouracil (5-FU).
      Results   Elevated levels of p-EZH2S21 were observed in HNSCC tissues and positively correlated with p-STAT3Y705 (P<0.05) and HIF-1α (P<0.01) levels. p-EZH2S21 level correlated positively with lymph node metastasis (P<0.000 5), T (P<0.05), N (P<0.000 1) and AJCC stages (P<0.05). In vitro experiments confirmed that EZH2 expression promoted cell proliferation and attenuated chemosensitivity of HNSCC cells. Inhibition of p-EZH2S21 restored HNSCC cell sensitivity to DDP and 5-FU.
      Conclusions   p-EZH2S21 plays an important role in tumor progression in HNSCC, and phosphorylation at S21 is an important way for EZH2 to affect HNSCC cell proliferation and chemotherapy sensitivity.

     

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