Transcriptomic biomarkers for individual risk assessment in new-onset heart failure
Transcriptomic biomarkers for individual risk assessment in new-onset heart failure
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DOI：
10.1161/circulationaha.107.756544
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发表时间：
2008-07-15
期刊：
影响因子：
37.8
通讯作者：
Hare, Joshua M.
中科院分区：
文献类型：
--
作者：
Heidecker, Bettina;Kasper, Edward K.;Hare, Joshua M.
背景-预测新发心力衰竭（HF）的预后仍然是一个主要的未满足的需求。虽然有几种临床试验正在使用中，但没有一种能准确区分患者的生存率差与生存率高。我们假设，一个转录组签名，从一个单一的endomyoestrophic活检，可以作为一种新的预后生物标志物在HF.Methods和结果endomyoestrophic活检样本和临床数据收集从1997年至2006年新发HF的所有患者。在总共350个肌内膜活检样本中，180个被确定为特发性扩张型心肌病。选择生存率表型极端的患者：预后良好（无事件生存至少5年; n = 25）和预后不良（在出现HF症状的前2年内发生事件[死亡、需要左心室辅助装置或心脏移植]; n = 18）。我们使用人类U133 Plus 2.0微阵列（Affyoung），并通过微阵列的显著性分析和微阵列的预测分析来分析数据。我们确定了46个过度表达的基因，患者预后好与预后差，其中45个基因是通过预测分析的微阵列预测预后的训练集（n = 29），随后验证测试集（n = 14）。生物标志物进行74%的灵敏度（95%CI 69%至79%）和90%的特异性（95%CI 87%至93%）后，50随机partitions. Conclusions，这些研究结果表明，潜在的转录生物标志物，以预测从一个单一的子宫内膜异位症活检样本新发HF患者的预后。此外，我们的研究结果为HF和心肌病提供了潜在的新治疗靶点。
Background-Prediction of prognosis remains a major unmet need in new-onset heart failure (HF). Although several clinical tests are in use, none accurately distinguish between patients with poor versus excellent survival. We hypothesized that a transcriptomic signature, generated from a single endomyocardial biopsy, could serve as a novel prognostic biomarker in HF.Methods and Results-Endomyocardial biopsy samples and clinical data were collected from all patients presenting with new-onset HF from 1997 to 2006. Among a total of 350 endomyocardial biopsy samples, 180 were identified as idiopathic dilated cardiomyopathy. Patients with phenotypic extremes in survival were selected: good prognosis (event-free survival for at least 5 years; n = 25) and poor prognosis (events [death, requirement for left ventricular assist device, or cardiac transplant] within the first 2 years of presentation with HF symptoms; n = 18). We used human U133 Plus 2.0 microarrays (Affymetrix) and analyzed the data with significance analysis of microarrays and prediction analysis of microarrays. We identified 46 overexpressed genes in patients with good versus poor prognosis, of which 45 genes were selected by prediction analysis of microarrays for prediction of prognosis in a train set (n = 29) with subsequent validation in test sets (n = 14 each). The biomarker performed with 74% sensitivity (95% CI 69% to 79%) and 90% specificity (95% CI 87% to 93%) after 50 random partitions.Conclusions-These findings suggest the potential of transcriptomic biomarkers to predict prognosis in patients with new-onset HF from a single endomyocardial biopsy sample. In addition, our findings offer potential novel therapeutic targets for HF and cardiomyopathy.