Wang Yi-Fen, Lin Yi-Ke, Lin Chin-Ping, Chen Yu-Jen, Chang Chun-Ju
Department of Otorhinolaryngology and Head and Neck Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.
Department of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Front Oncol. 2021 Mar 30;11:646167. doi: 10.3389/fonc.2021.646167. eCollection 2021.
A low NM23-H1 expression in head and neck squamous cell carcinoma (HNSCC) was found to be associated with poor clinical outcome. Therefore, we investigated the role of NM23-H1 in the susceptibility of HNSCC cells to irradiation and its clinical significance. An study was also conducted to validate the results. Furthermore, we used immunohistochemistry to analyze NM23-H1 expression found in specimens of 50 HNSCC patients with cervical metastases receiving postoperative radiotherapy. Low tumor NM23-H1 expression was associated with locoregional recurrence of HNSCC (p=0.040; Hazard ratio=5.62) and poor clinical outcome (p=0.001; Hazard ratio=4.90). To confirm the effect of NM23-H1 on radiation-induced cytotoxicity, we generated several stable clones derived from a human HNSCC cell line (SAS) using knockdown and overexpression of NM23-H1. Knockdown of NM23-H1 decreased the radio-sensitivity of SAS cells, possibly associated with a decrease in the radiation-induced G2/M-phase accumulation and upregulation of cyclin B1. On the contrary, overexpression of NM23-H1 can reverse the aforementioned adverse results. Consequently, we suggest that NM23-H1 expression may be considered as a potential therapeutic treatment option for HNSCC patients.
研究发现,头颈部鳞状细胞癌(HNSCC)中NM23-H1低表达与不良临床预后相关。因此,我们研究了NM23-H1在HNSCC细胞对辐射敏感性中的作用及其临床意义。还进行了一项研究以验证结果。此外,我们采用免疫组织化学方法分析了50例接受术后放疗的伴有颈部转移的HNSCC患者标本中NM23-H1的表达情况。肿瘤NM23-H1低表达与HNSCC的局部区域复发(p=0.040;风险比=5.62)及不良临床预后(p=0.001;风险比=4.90)相关。为证实NM23-H1对辐射诱导的细胞毒性的影响,我们通过敲低和过表达NM23-H1,从人HNSCC细胞系(SAS)中获得了几个稳定克隆。敲低NM23-H1降低了SAS细胞的放射敏感性,这可能与辐射诱导的G2/M期阻滞减少和细胞周期蛋白B1上调有关。相反,过表达NM23-H1可逆转上述不良结果。因此,我们认为NM23-H1表达可作为HNSCC患者一种潜在的治疗选择。