Department of Otorhinolaryngology, Head and Neck Surgery, University of Chinese Academy of Sciences, Shenzhen Hospital, Shenzhen, China.
Department of Otorhinolaryngology, Head and Neck Surgery, Affiliated Xinhua Hospital of Hainan Medical Colleage, Haikou, China.
J Physiol Pharmacol. 2022 Feb;73(1). doi: 10.26402/jpp.2022.1.12. Epub 2022 Jul 4.
Nasopharyngeal carcinoma (NPC) is a common malignancy in Southern China and Southeast Asia. Radiotherapy is the main treatment option. However, radiotherapy does not benefit all patients because there is no known precise biomarker that can be used for screening radioresistant patients. Genetic predisposition is closely related to tumor development, therapeutic response, and prognosis. The relationship between regenerating gene IA (REGIA) and NPC is unclear. This study aimed to retrospectively analyze the association between REGIA expression and metastasis, radiosensitivity, and survival in patients with NPC as well as assess the effect of radiation on REGIA expression in vitro. Immunohistochemical staining was used to detect REGIA. The relationship between REGIA expression in radioresistant NPC and the prognosis of CNE1 NPC cells were analyzed using quantitative real-time polymerase chain reaction and Western blotting. We found that increased doses of radiation in CNE1 cells significantly decreased REGIA expression (P<0.05). The overall rate of REGIA-positive expression was 47.15% in NPC tissues and 45.00% and 61.02% in radiosensitive and radioresistant cases, respectively, showing significant differences (P<0.05). A REGIA-positive protein expression rate had a negative correlation with radiosensitivity in NPC (r= -0.109, P=0.047). Both REGIA-positive and REGIA-negative expression strongly predicted the overall survival rate and progression-free survival of NPC patients (P<0.01). A multivariate analysis indicated that REGIA was an inverse prognostic factor in NPC patients (REGIA-positive expression: hazard ratio (HR)=2.139, 95% confidence interval (CI)=1.56-2.94, P<0.001 and REGIA-negative expression: HR=1.958, 95% CI=1.42-2.69, P<0.001). In conclusion: Radiation can affect REGIA expression. The REGIA expression level correlated with radioresistance and a poor prognosis. In addition, REGIA expression might act as a potential therapeutic target and prognostic predictor in NPC patients.
鼻咽癌（NPC）是中国南方和东南亚地区常见的恶性肿瘤。放射治疗是主要的治疗选择。然而，放射治疗并不适用于所有患者，因为目前还没有已知的精确生物标志物可用于筛选放射抗拒患者。遗传易感性与肿瘤的发生、治疗反应和预后密切相关。再生基因 IA（REGIA）与 NPC 之间的关系尚不清楚。本研究旨在回顾性分析 REGIA 表达与 NPC 患者转移、放射敏感性和生存之间的关系，并评估体外放射对 REGIA 表达的影响。采用免疫组织化学染色检测 REGIA。采用定量实时聚合酶链反应和 Western blot 分析 NPC 中 REGIA 表达与 CNE1 NPC 细胞预后的关系。结果发现，CNE1 细胞中辐射剂量的增加显著降低了 REGIA 的表达（P<0.05）。NPC 组织中 REGIA 阳性表达率为 47.15%，放射敏感和放射抗拒病例分别为 45.00%和 61.02%，差异有统计学意义（P<0.05）。NPC 中 REGIA 阳性蛋白表达率与放射敏感性呈负相关（r=-0.109，P=0.047）。REGIA 阳性和 REGIA 阴性表达均强烈预测 NPC 患者的总生存率和无进展生存率（P<0.01）。多因素分析表明，REGIA 是 NPC 患者的预后不良因素（REGIA 阳性表达：风险比（HR）=2.139，95%置信区间（CI）=1.56-2.94，P<0.001；REGIA 阴性表达：HR=1.958，95%CI=1.42-2.69，P<0.001）。结论：辐射可影响 REGIA 的表达。REGIA 的表达水平与放射抵抗和不良预后相关。此外，REGIA 表达可能成为 NPC 患者潜在的治疗靶点和预后预测因子。
