尿液细胞mRNA联合生物标志物对IgA肾病肾纤维化诊断价值研究

Diagnostic value of combined model of urinary-cell mRNA biomarkers for renal fibrosis in IgA nephropathy

目的:筛选诊断IgA肾病肾纤维化的新型无创生物标志物。方法:建立IgA肾病靶向实时荧光聚合酶链式扩增反应芯片,检测74例IgA肾病患者和31例健康对照的尿液mRNA,筛选差异表达基因建立联合生物标志物预测肾纤维化模型。结果:50种尿液mRNA在IgA肾病组和对照组之间差异表达(P<0.05)。5种mRNA与血肌酐和肾小球滤过率相关(P<0.05)。BCL-2、PAI1、TGF-β1和VIM mRNA水平与肾纤维化的严重程度相关,并且能区分中-重度纤维化和无-轻度纤维化(P<0.05)。使用Fisher线性判别建立BCL-2、PAI1、TGF-β1、VIM联合生物标志物预测模型,其敏感性91.3%,特异性85.7%,ROC曲线下面积0.92,约登指数0.77(P<0.05)。结论:4种尿液mRNA组成的无创生物标志物具备诊断IgA肾病肾纤维化的潜力。

Objective:To screen new non-invasive biomarkers of renal fibrosis(RF)in IgA nephrology(IgAN).Methods:PCR array was established and urinary cell mRNAs of 74 IgAN patients and 31 healthy controls was measured.Differentially expressed genes were identified to establish a combined biomarker prediction model for RF.Results:There were 50 mRNAs differentially expressed between the IgAN group and the control group.And 5 mRNAs were correlated with Scr and eGFR(P<0.05).Expression levels of BCL-2,PAI1,TGF-β1,and VIM mRNA were correlated with RF severity and could effectively distinguish moderate-severe fibrosis from none-mild fibrosis(P<0.05).Fisher linear discriminant analysis was used to establish the combined prediction model of BCL-2,PAI1,TGF-β1 and VIM biomarker,with the sensitivity was 91.3%,specificity was 85.7%,the largest AUC was 0.92,and the best Youden's index was 0.77(P<0.05).Conclusion:Non-invasive biomarkers composed of four urinary mRNAs have the potential to diagnose RF in IgAN patients.