【摘要】 目的:发现激素性股骨头坏死(SONFH)不同中医证型分子标志。方法:60例SONFH组患者与20例接受激素治疗未发生股骨头坏死的对照组患者随机分为训练集与验证集。通过全基因组表达谱芯片检测与生物分子网络分析相整合的方法,筛选SONFH不同证型候选分子标志,进而构建辨证预测模型。采用大规模独立样本测试和十倍交叉验证评估上述辨证预测模型的准确性与稳定性。结果:本研究分别获得4个痰瘀阻络证(CD28、CD4、PLCG1、PRKCA)、4个经脉痹阻证(PTGS2、SOS2、STAT6、TLR4)和5个肝肾亏虚证(IFIT1、IRF7、ISG15、MAPK14、RHOU)的候选标志基因,显著参与抑制成骨细胞分化、破骨细胞发育、炎症免疫反应等与SONFH病理改变相关生物学反应。基于上述候选基因在患者外周血中的表达量所建立的辨证预测模型,经十倍交叉验证和独立样本集验证表明,其最优辨证准确性均在83%以上,受试者工作特征曲线下面积均大于0.800。结论:3种SONFH证型预测模型的性能良好且稳定,为揭示SONFH"三期四型"的生物学基础提供客观依据。更多还原

【Abstract】 Objective: To identify potential biomarkers for the different syndromes of steroid-induced osteonecrosis of the femoral head(SONFH). Methods: A total of 60 SONFH patients and 20 controls were enrolled in the present study. All the samples were divided into a discovery cohort and validation cohort(40 per group) randomly. The gene expression profile was detected by microarray analysis based on the discovery cohort. Then, the syndrome-related molecular interaction networks were constructed to identify potential biomarkers of different syndromes. The efficiency of three syndrome differentiation models of SONFH was evaluated by cross-validation and independent dataset validation. Results: Totally, we respectively identified four stagnation of phlegm and blood stasis syndrome markers(CD28, CD4, PLCG1, PRKCA), four blockages of channels syndrome markers(PTGS2, SOS2, STAT6, TLR4) and five deficiency of liver and kidney syndrome markers(IFIT1, IRF7, ISG15, MAPK14, RHOU). In addition, the syndrome differentiation models of three different syndromes were constructed based on the serum levels of the above marker genes. Both the cross-validation and the independent dataset validation indicated that the accuracy of the highest model over 83%, receiver operating characteristic greater than 0.800. Conclusion: The three SONFH syndrome prediction models have good and stable performance, which provides an objective basis for revealing the biological basis of ‘three stages and four types’ of SONFH.更多还原