ARMD出血患者血清miR-27a和NRF2的表达与预后的相关性

目的：检测年龄相关性黄斑变性(ARMD)出血患者血清微小RNA-27a(miR-27a)和转录因子E2相关因子(NRF2)的表达情况，并研究其相对表达量与ARMD出血患者预后的相关性。

方法：采用回顾性病例对照研究，收集2018-06/2019-10在本院眼科确诊并治疗的ARMD出血患者80例为ARMD出血组，选取同期在本院进行常规检查的健康受试者80例为对照组。采用实时荧光定量PCR法(qRT-PCR)检测所有研究对象血清miR-27a和NRF2相对表达量； 通过研究对象工作特征曲线(ROC)评估血清miR-27a和NRF2相对表达量对ARMD出血的诊断价值； 分析患者预后不良情况发生率； 采用Logistic回归分析ARMD出血患者预后不良的影响因素。

结果：ARMD出血患者血清miR-27a相对表达量显著高于对照组(P<0.01)，血清NRF2 mRNA相对表达量显著低于对照组(P<0.01)。ROC结果显示，血清miR-27a和NRF2诊断ARMD出血的AUC分别为0.867、0.820，截断值分别为1.10、1.08，此时对应灵敏度分别为71.3%、91.3%，特异性分别为90.0%、63.7%。血清miR-27a和NRF2联合检测ARMD出血的AUC为0.912，此时对应灵敏度和特异性分别为86.3%、85.0%。高miR-27a组患者预后不良发生率明显高于低miR-27a组(P<0.05)； 高NRF2组患者预后不良发生率显著低于低NRF2组(P<0.05)。Logistic分析显示，血清miR-27a高表达是影响ARMD出血患者发生预后不良的危险因素，血清NRF2高表达是影响ARMD出血患者发生预后不良的保护因素。

结论：miR-27a在ARMD出血患者血清中的相对表达量明显升高，NRF2相对表达量明显降低，两者对ARMD出血具有一定诊断价值，且其表达情况与患者预后密切相关，提示血清miR-27a和NRF2可作为ARMD出血的早期诊断及预后评估的潜在生物学指标。

Expressions of miR-27a and NRF2 in serum of patients with age-related macular degeneration bleeding and their prognostic correlation

AIM: To detect the relative expression levels of microRNA-27a(miR-27a)and nuclear factor erythroid-2-related factor 2(NRF2)in serum of patients with age-related macular degeneration(ARMD)bleeding, and to explore the correlation between the expression levels and the prognosis of ARMD bleeding.

METHODS: A retrospective case series observation was carried out.From June 2018 to October 2019, 80 patients with ARMD bleeding who were treated in our hospital were selected as ARMD bleeding group, and 80 healthy people who had routine examination in our hospital were selected as control group. The relative expression levels of miR-27a and NRF2 were detected by real-time fluorescent quantitative PCR(qRT-PCR), the diagnostic value of serum miR-27a and NRF2 expression for ARMD bleeding was evaluated by receiver operating characteristic curve(ROC). The incidence of poor prognosis was analyzed; in addition, Logistic regression was used to analyze the influencing factors of poor prognosis in patients with ARMD bleeding.

RESULTS: The relative expression level of miR-27a in serum of ARMD bleeding group was significantly higher than that of control group(P<0.01), and the relative expression level of NRF2 mRNA in serum was significantly lower than that in control group(P<0.01). ROC results showed that the AUC of serum miR-27a and NRF2 in the diagnosis of ARMD bleeding was 0.867 and 0.820 respectively, and the cutoff value was 1.10 and 1.08 respectively, at this time, the corresponding sensitivity was 71.3% and 91.3%, and the specificity was 90.0% and 63.7%, respectively. The AUC of serum miR-27a combined with NRF2 in the diagnosis of ARMD bleeding was 0.912, and the corresponding sensitivity and specificity were 86.3% and 85.0%, respectively. The incidence of poor prognosis in high miR-27a group was significantly higher than that in low miR-27a group(P<0.05); and the incidence of poor prognosis in high NRF2 group was significantly lower than that in low NRF2 group(P<0.05). Logistic analysis showed that the high expression of serum miR-27a was an independent risk factor for poor prognosis in patients with ARMD bleeding, and the high relative expression of NRF2 in serum was a protective factor for the poor prognosis of patients with ARMD bleeding.

CONCLUSION: The relative expression level of miR-27a in the serum of patients with ARMD hemorrhage is significantly increased, and the relative expression level of NRF2 is significantly decreased, both of them have certain diagnostic value for ARMD bleeding, and their relative expressions are closely related to the prognosis of patients, which is suggested that miR-27a and NRF2 can be used as potential biological indexes for early diagnosis and prognosis evaluation of ARMD bleeding.