IgA肾病患者血清Rho相关卷曲螺旋形成蛋白激酶2、视黄醇结合蛋白4表达水平及在评估病情和预测预后中的价值研究

    Serum expression levels of rho-associated coiled-coil containing protein kinase 2 and retinol-binding protein 4 in patients with IgA nephropathy and their values in evaluating disease condition and predicting prognosis

      摘要
    • 摘要:
      目的  检测IgA肾病（immunoglobulin A nephropathy，IgAN）患者血清Rho相关卷曲螺旋形成蛋白激酶2（rho associated coiled coil containing protein kinase 2，ROCK2）、视黄醇结合蛋白4（retinol-binding protein 4，RBP4）表达水平，分析二者在评估患者病情及预测预后中的价值。
      方法  选取2016年6月至2019年6月98例中国贵航集团302医院已确诊收治的IgAN患者为IgAN组，其中轻度IgAN 36例、中度IgAN 32例、重度IgAN 30例；同期选择在中国贵航集团302医院体检的健康者100名为对照组。酶联免疫吸附法检测血清中ROCK2、RBP4水平；采用Kaplan-Meier生存曲线分析ROCK2、RBP4表达水平与IgAN患者预后的关系；Pearson相关性分析ROCK2与RBP4表达相关性；受试者工作特征曲线（receiver operating characteristic curve，ROC）分析ROCK2、RBP4对IgAN的诊断价值；比例风险回归模型法分析IgAN患者预后的影响因素。
      结果  IgAN组血清中ROCK2、RBP4表达水平分别为（24.25 ± 5.31）μg/L、（59.70 ± 9.43）μg/L，显著高于对照组的（15.57 ± 4.16）μg/L、（32.14 ± 7.82）μg/L，差异具有统计学意义（t=12.818、22.404，均P＜0.001）；轻度、中度、重度IgAN患者血清中ROCK2水平分别为（18.69 ± 4.36）μg/L、（23.75 ± 5.31）μg/L、（31.46 ± 5.62）μg/L，RBP4表达水平分别为（45.37 ± 7.86）μg/L、（62.48 ± 8.12）μg/L、（73.94 ± 8.65）μg/L。随着病情的加重，IgAN患者血清ROCK2、RBP4表达水平逐渐升高，差异具有统计学意义（F=51.854、102.234，均P＜0.05）；IgAN患者血清中ROCK2、RBP4表达水平与Lee氏分级、IgA/C3比值、病情程度有关（P＜0.05）；ROCK2、RBP4高表达组患者预后生存率分别为60.00%、74.19%，均显著低于低表达组的89.71%、91.67%，差异具有统计学意义（log rank χ2=4.674，P=0.031）；ROC曲线结果显示，血清ROCK2诊断IgAN的曲线下面积（area under curve，AUC）为0.889，敏感度为80.61%，特异性为80.00%，截断值为18.79 μg/L；RBP4诊断IgAN的AUC为0.986，敏感度为96.94%，特异性为95.00%，截断值为41.31 μg/L；二者联合检测的AUC为0.997，敏感度为98.98%，特异性为94.86%。Pearson相关性分析显示，IgAN患者血清ROCK2与RBP4表达水平呈显著正相关（r=0.701，P＜0.001）；多因素比例风险回归模型法分析表明，IgA/C3（OR=2.683，95%CI：1.060～6.794）、ROCK2（OR=1.831，95%CI：1.027～3.264）、RBP4（OR=1.517，95%CI：1.104～2.084）均是IgAN患者预后生存的影响因素（均P＜0.05）。
      结论  ROCK2、RBP4在IgAN患者血清中高表达，二者与IgAN患者的临床病理特征、病情严重程度及预后关系密切，ROCK2、RBP4表达水平对IgAN的诊断具有一定的价值。

       

      Abstract:
      Objective  To detect the expression levels of rho-associated coiled-coil containing protein kinase 2 （ROCK2） and retinol-binding protein 4 （RBP4） and examine the value of ROCK2/RBP4 in evaluating disease condition and predicting prognosis in patients with immunoglobulin A nephropathy （IgAN）.
      Methods  From June 2016 to June 2019, 98 IgAN patients were selected as IgAN group, including mild IgAN （n=36）, moderate IgAN （n=32） and severe IgAN （n=30）. And 100 healthy subjects receiving physical examination during the same period were designated as control group. Serum levels of ROCK2 and RBP4 were detected by enzyme-linked immunosorbent assay （ELISA）. Kaplan-Meier survival curve was plotted for examining the relationship between the expression level of ROCK2/RBP4 and prognosis; Pearson's method was employed for analyzing the correlation between ROCK2 and RBP4 expressions; Receiver operating characteristic curve （ROC） for examining the diagnostic value of ROCK2/RBP4 for IgAN; COX method for analyzing the prognostic factors.
      Results  The serum expression levels of ROCK2 and RBP4 were significantly higher in IgAN group than those in control group （24.25 ± 5.31） μg/L, （59.70 ± 9.43） μg/L vs （15.57 ± 4.16） μg/L, （32.14 ± 7.82） μg/L）. The difference was statistically significant （t=12.818, 22.404, all P＜0.001）. The serum expression levels of ROCK2 and RBP4 were （18.69 ± 4.36） μg/L vs （23.75 ± 5.31） μg/L, （31.46 ± 5.62） μg/L vs （45.37 ± 7.86） μg/L and （62.48 ± 8.12） μg/L vs （73.94 ± 8.65） μg/L in mild/moderate/severe IgAN patients. With the worsening of disease, the expression levels of serum ROCK2 and RBP4 were up-regulated and the difference was statistically significant （F=51.854, 102.234, all P＜0.05）. The serum expression levels of ROCK2 and RBP4 were correlated with Lee's grade, IgA/C3 ratio and disease severity （P＜0.05）; The prognosis survival rates of patients with a high expression of ROCK2/RBP4 were significantly lower than those with a low expression of ROCK2/RBP4 （60.00% vs 74.19%, 89.71% vs 91.67%） and the difference was statistically significant （Log rank=4.674, P=0.031）; ROC curve results indicated that AUC of serum level of ROCK2 for diagnosing IgAN was 0.889 with a sensitivity of 80.61%, a specificity of 80.00% and a cut-off value of 18.79 μg/L; AUC of RBP4 for diagnosing IgAN was 0.986 with a sensitivity of 96.94%, a specificity of 95.00% and a cut-off value of 41.31 μg/L; AUC of the combined detection was 0.997 with a sensitivity of 98.98% and a specificity of 94.86%. Pearson’s correlation analysis revealed that the serum expression levels of ROCK2 and RBP4 were correlated positively （r=0.701, P＜0.001）; Multivariate COX regression analysis revealed that IgA/C3 （OR=2.683, 95%CI :1.060-6.794）, ROCK2 （OR=1.831, 95%CI :1.027-3.264） and RBP4 （OR=1.517, 95%CI : 1.104-2.084） were the influencing factors of prognosis and survival in IgAN patients （all P＜0.05）.
      Conclusion  ROCK2 and RBP4 are highly expressed in sera of IgAN patients. Both are correlated closely with the clinicopathological characteristics, disease severity and prognosis of IgAN patients. The expression levels of ROCK2 and RBP4 have some diagnostic values.

       

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