Transcriptomic biomarkers for the accurate diagnosis of myocarditis.
Transcriptomic biomarkers for the accurate diagnosis of myocarditis.
复制标题
DOI：
10.1161/circulationaha.110.002857
复制
发表时间：
2011-03-22
期刊：
影响因子：
37.8
通讯作者：
Hare JM
中科院分区：
文献类型：
--
作者：
Heidecker B;Kittleson MM;Kasper EK;Wittstein IS;Champion HC;Russell SD;Hruban RH;Rodriguez ER;Baughman KL;Hare JM
淋巴细胞性心肌炎是一种临床上很重要的疾病，很难诊断和区分。我们假设从子宫内膜活检（EMB）获得的转录组将产生临床相关和准确的分子特征。对来自组织学证实的淋巴细胞性心肌炎（n=16）和特发性扩张型心肌病（IDCM，n=32）患者的样本进行微阵列分析，以使用多种分类算法开发准确的诊断性基于转录组的生物标志物（TBB）。我们鉴定了9,878个在淋巴细胞性心肌炎和IDCM中差异表达的基因。（FC>1.2，FDR<5%），从中鉴定出含有62个基因的TBB，其以100%的灵敏度区分心肌炎（95% CI：46-100%）和100%特异性（95%置信区间：66-100%），并且可推广到与炎症相关的广泛继发性心肌病（n=27），缺血性心肌病（n=8）和正常心脏（n=11）。多重分类算法和定量实时RT-PCR分析进一步将该子集减少到13个基因的高度稳健的分子特征，其仍然以100%的准确性进行。总之，这些发现表明，来自单个EMB的转录组学生物标志物可以改善患有心脏炎性疾病的患者的临床检测。这种方法推进了具有高度可变结局的心脏疾病的临床管理和治疗。
Lymphocytic myocarditis is a clinically important condition that is difficult to diagnose and distinguish. We hypothesized that the transcriptome obtained from an endomyocardial biopsy (EMB) would yield clinically relevant and accurate molecular signatures. Microarray analysis was performed on samples from patients with histologically proven lymphocytic myocarditis (n=16) and idiopathic dilated cardiomyopathy (IDCM, n=32) to develop accurate diagnostic transcriptome-based biomarkers (TBB) using multiple classification algorithms. We identified 9,878 genes differentially expressed in lymphocytic myocarditis vs. IDCM (FC>1.2, FDR<5%), from which a TBB containing 62 genes was identified, which distinguished myocarditis with 100% sensitivity (95% CI: 46-100%) and 100% specificity (95% CI: 66-100%) and which was generalizable to a broad range of secondary cardiomyopathies associated with inflammation (n=27), ischemic cardiomyopathy (n=8) and the normal heart (n=11). Multiple classification algorithms and quantitative realtime RT-PCR analysis further reduced this subset to a highly robust molecular signature of 13 genes, which still performed with 100% accuracy. Together these findings demonstrate that transcriptomic biomarkers from a single EMB can improve the clinical detection of patients with inflammatory diseases of the heart. This approach advances the clinical management and treatment of cardiac disorders with highly variable outcome.