EBV编码的miR-BART8-3p与鼻咽癌放疗抵抗的相关性分析-东南大学学报医学版

EBV编码的miR-BART8-3p与鼻咽癌放疗抵抗的相关性分析

单位：玉林市第一人民医院耳鼻咽喉科, 广西玉林 537000

分类号：R739.6;R730.55

出版年·卷·期（页码）：2022·41·第三期（371-379）

摘要：

目的：探究EB病毒（EBV）编码的miR-BamHI-A区右向转录（BART）8-3p（EBV-miR-BART8-3p）与鼻咽癌（NPC）放疗抵抗的相关性。方法：选取2018年7月至2020年7月本院104例初诊NPC患者（NPC组），另选取同期100例慢性鼻窦炎鼻息肉患者（良性病变组），比较两组患者血浆和组织EBV-miR-BART8-3p表达水平。分析NPC患者血浆和组织EBV-miR-BART8-3p表达水平在临床病理特征、放疗效果中的差异，采用受试者工作特征（ROC）曲线分析血浆EBV-miR-BART8-3p水平对NPC患者发生放疗抵抗的预测价值。结果：NPC组血浆和组织EBV-miR-BART8-3p表达水平均显著高于良性病变组（P<0.001）。9例EBV-DNA阴性NPC患者血浆和组织EBV-miR-BART8-3p表达水平低于EBV-DNA阳性者；经Pearson相关系数分析，EBV-DNA阳性NPC患者血浆与组织EBV-miR-BART8-3p表达水平呈正相关，且两者与EBV-DNA拷贝数亦呈正相关（r值分别为0.452、0.717、0.726，均P<0.001）。T3~T4期、N0期、美国东部肿瘤协作组（ECOG）状态评分为2分患者的组织EBV-miR-BART8-3p表达水平更高（均P<0.05）；T3~T4期、TNM Ⅲ~Ⅳ期、EBV衣壳抗原（VCA）-IgA为阳性患者的血浆EBV-miR-BART8-3p表达水平更高（均P<0.05）。放疗抵抗患者组织和血浆EBV-miR-BART8-3p表达水平显著高于放疗敏感者（P<0.05）。经多因素Logistic回归分析，血浆EBV-miR-BART8-3p表达水平>1.731和组织EBV-miR-BART8-3p表达水平>2.850是NPC患者发生放疗抵抗的独立危险因素（P<0.05）。经ROC曲线分析，血浆和组织EBV-miR-BART8-3p表达水平预测NPC患者发生放疗抵抗的曲线下面积（AUC）分别为0.915（95%CI：0.862~0.968）、0.889（95%CI：0.814~0.964）。结论：NPC患者血浆和组织EBV-miR-BART8-3p表达水平升高与放疗抵抗风险有关。

Objective: To investigate the correlation between Epstein-Barr virus(EBV)-encoded BamHI-A rightward transcripts(BART) 8-3p(EBV-miR-BART8-3p) and the radioresistance of nasopharyngeal carcinoma(NPC). Methods: One hundred and four newly diagnosed NPC patients in our hospital from July 2018 to July 2020 were selected as NPC group, and another 100 patients with chronic sinusitis and nasal polyps during the same period were selected as benign lesion group to compare their EBV-miR-BART8-3p expression in tissues and plasma. The relationship between the plasma and tissue EBV-miR-BART8-3p expression and clinicopathological characteristics and radioresistance in NPC patients was analyzed. Receiver operating characteristic(ROC) curve was used to analyze predictive value of plasma EBV-miR-BART8-3p expression on radioresistance in NPC patients. Results: The EBV-miR-BART8-3p expression in plasma and tissue of NPC patients was significantly higher than that of benign lesion group(P<0.001). The EBV-miR-BART8-3p expression in plasma and tissue of 9 cases of EBV-DNA negative NPC patients was lower than that of the EBV-DNA positive ones. Pearson analysis showed that the EBV-miR-BART8-3p expression in plasma and tissues of EBV-DNA positive NPC patients had positive correlation, and both were also positively correlated with the EBV-DNA copy numbers(r=0.452, 0.717, 0.726, P<0.001). EBV-miR-BART8-3p expression level was higher in the tissue of patients with T stage T3 to T 4, N stage N0, and Eastern Cooperative Oncology Group(ECOG) status score of 2(P<0.05). The plasma EBV-miR-BART8-3p expression was higher in patients with T stage T3-T4, TNM stage Ⅲ-Ⅳ and EBV capsid antigen(VCA)-IgA was positive(P<0.05). The EBV-miR-BART8-3p expression in tissue and plasma of radioresistance patients was significantly higher than that of radiosensitive patients(P<0.05). Multivariate Logistic regression analysis showed that both plasma EBV-miR-BART8-3p expression>1.731 and tissue EBV-miR-BART8-3p expression>2.850 were the independent risk factors for radioresistance in NPC patients(P<0.05). According to ROC curve analysis, the AUC of plasma and tissue EBV-miR-BART8-3p expression levels predicted to develop radioresistance was 0.915(95%CI:0.862-0.968) and 0.889(95%CI:0.814-0.964)in NPC patients, respectively. Conclusion: The increased plasma and tissue EBV-miR-BART8-3p expression in NPC patients can be correlated with the occurrence of radioresistance.

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