外周血单个核细胞circRNA SLAIN1和PSEN1诊断帕金森病价值

Values of circular RNA SLAIN1 and PSEN1 in peripheral blood mononuclear cells to the diagnosis of Parkinson’s disease

目的观察帕金森病(Parkinson’s disease,PD)患者外周血单个核细胞circRNA SLAIN1、PSEN1表达变化,探讨二者诊断PD的价值。方法80例PD患者为PD组,依据Hoehn-Yahr分级分为轻度组28例,中度组28例,重度组24例;同期体检健康者50例为对照组。比较PD组与对照组简易精神状态检查量表(mini-mental state examination,MMSE)评分及合并高血压、糖尿病比率等;采用实时荧光定量PCR法检测外周血单个核细胞circRNA SLAIN1、PSEN1相对表达量;Pearson相关法分析PD患者circRNA SLAIN1、PSEN1表达与帕金森病评定量表(unified Parkinson’s disease rating scale,UPDRS)Ⅰ、Ⅱ、Ⅲ评分的相关性;绘制ROC曲线,评估circRNA SLAIN1、PSEN1单独及联合检测对PD的诊断效能。结果PD组年龄,MMSE评分,男性及合并高血压、糖尿病比率与对照组比较差异均无统计学意义(P>0.05)。PD组circRNA SLAIN1、PSEN1相对表达量(1.57±0.34、1.48±0.35)均低于对照组(6.22±0.83、5.19±0.90)(t=44.560,P<0.001;t=33.137,P<0.001)。轻度组circRNA SLAIN1、PSEN1相对表达量(2.34±0.41、2.42±0.45)均高于中度组(1.52±0.35、1.45±0.33)和重度组(0.73±0.24、0.42±0.25)(P<0.05),中度组高于重度组(P<0.05)。PD患者circRNA SLAIN1表达与UPDRSⅠ、Ⅱ、Ⅲ评分均呈负相关(r=—0.495,P<0.001;r=—0.437,P<0.001;r=—0.512,P<0.001),PSEN1表达与UPDRSⅠ、Ⅱ、Ⅲ评分均呈负相关(r=—0.484,P<0.001;r=—0.476,P<0.001;r=—0.503,P<0.001)。circRNA SLAIN1、PSEN1相对表达量分别以1.50、1.45为最佳截断值,诊断PD的AUC分别为0.809(95%CI:0.749~0.869,P<0.001)、0.849(95%CI:0.790~0.908,P<0.001),灵敏度分别为86.3%、75.6%,特异度分别为73.7%、82.7%;二者联合诊断PD的AUC为0.963(95%CI:0.926~0.989,P<0.001),灵敏度为92.2%,特异度为80.6%;二者联合诊断PD的AUC大于二者单独检测(Z=4.829,P<0.001;Z=3.557,P<0.001)。结论PD患者外周血单个核细胞circRNA SLAIN1、PSEN1表达降低,其表达越低提示病情越严重,二者联合检测诊断PD有较高价值。

Objective To observe the expressions of circular RNA(circRNA)SLAIN1and PSEN1in peripheral blood mononuclear cells of Parkinson’s disease(PD)patients,and to explore their predictive values.Methods Eighty PD patients(PD group)were divided into mild group(n=28),moderate group(n=28)and severe group(n=24)according to Hoehn-Yahr classification.And another 50healthy volunteers during the same period were selected as control group.The mini-mental state examination(MMSE)score and percentages of patients with hypertension and diabetes were compared between PD group and control group.The relative expressions of circRNA SLAIN1and PSEN1were detected by real-time fluorescence quantitative PCR.Pearson correlation method was used to analyze the correlations of the relative expressions of circRNA SLAIN1and PSEN1with the unified Parkinson’s disease rating scale(UPDRS)Ⅰ,Ⅱ and Ⅲ scores in PD group.ROC curve was drawn to evaluate the values of single and combined detection of circRNA SLAIN1and PSEN1to the diagnosis of PD.Results There were no significant differences in the age,MMSE score,and percentages of male patients and patients with hypertension and diabetes between PD group and control group(P>0.05).The relative expressions of circRNA SLAIN1and PSEN1were lower in PD group(1.57±0.34,1.48±0.35)than those in control group(6.22±0.83,5.19±0.90)(t=44.560,P<0.001;t=33.137,P<0.001),were higher in mild group(2.34±0.41,2.42±0.45)than those in moderate group(1.52±0.35,1.45±0.33)and severe group(0.73±0.24,0.42±0.25)(P<0.05),and were higher in moderate group than those in severe group(P<0.05).The circRNA SLAIN1 in PD patients was negatively correlated with UPDRSⅠ,Ⅱ and Ⅲ scores(r=-0.495,P<0.001;r=-0.437,P<0.001;r=-0.512,P<0.001),and the circRNA PSEN1 was also negatively correlated with UPDRSⅠ,Ⅱ and Ⅲ scores(r=-0.484,P<0.001;r=-0.476,P<0.001;r=-0.503,P<0.001).When the optimal cut-offvalues of circRNA SLAIN1and PSEN1were 1.50and 1.45,the AUCs for diagnosing PD were 0.809(95%CI:0.749-0.869,P<0.001)and 0.849(95%CI:0.790-0.908,P<0.001),the sensitivities were 86.3% and 75.6%,and the specificities were 73.7%and 82.7%,respectively.The AUCof combined detection of them two was0.963(95%CI:0.926-0.989,P<0.001),higher than that of the single detection(Z=4.829,P<0.001;Z=3.557,P<0.001),with a sensitivity of 92.2%,and a specificity of 80.6%.Conclusions The circRNA SLAIN1 and PSEN1 in PD patients are lowly expressed,and the lower the expressions,the more serious the disease.The combined detection of them two has a high diagnostic value for PD.