Whole blood gene expression profiling predicts therapeutic response at six months in patients with polyarticular juvenile idiopathic arthritis.

Whole blood gene expression profiling predicts therapeutic response at six months in patients with polyarticular juvenile idiopathic arthritis.
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多关节特发性关节炎患者的六个月患者的全血基因表达谱分析可预测六个月的治疗反应。

DOI:
10.1002/art.38341
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发表时间:
2014-05
影响因子:
13.3
通讯作者:
Jarvis, James N.
Jarvis, James N.
中科院分区:
医学1区
文献类型:
--
作者:
Jiang, Kaiyu;Sawle, Ashley D.;Frank, M. Barton;Chen, Yanmin;Wallace, Carol A.;Jarvis, James N.

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确定外周全血样本中鉴定的基因表达谱是否可用于确定新诊断的多关节幼年特发性关节炎(JIA)儿童队列的治疗结果。在Illumina微阵列上分析来自JIA患者的早期侵袭性治疗试验(TREAT)的全血样品,并将差异基因表达与健康对照中的表达进行比较。在一个独立的样本队列中,通过实时定量聚合酶链反应验证微阵列结果。使用途径分析软件来表征基因表达谱。支持向量机用于开发不同患者类别的预测模型。类风湿因子(RF)阳性和RF阴性患者的差异基因表达谱非常相似。途径分析揭示了广泛的受影响的途径,符合目前的机制理论。建模显示,6个月时的预后与表现时的基因表达密切相关,与治疗无关。基因表达与治疗结果相关,外周血中的基因表达可能是预后检测的合适靶点。
To determine whether gene expression profiles identified in peripheral whole blood samples could be used to determine therapeutic outcome in a cohort of children with newly diagnosed polyarticular juvenile idiopathic arthritis (JIA). Whole blood samples from the Trial of Early Aggressive Therapy (TREAT) in JIA patients were analyzed on Illumina microarrays, and differential gene expression was compared to expression in healthy controls. Microarray results were validated by real-time quantitative polymerase chain reaction in an independent cohort of samples. Pathway analysis software was used to characterize gene expression profiles. Support vector machines were used to develop predictive models for different patient classes. Differential gene expression profiles for rheumatoid factor (RF)–positive and RF-negative patients were remarkably similar. Pathway analysis revealed a broad range of affected pathways, consistent with current mechanistic theories. Modeling showed that the prognosis at 6 months was strongly linked to gene expression at presentation, irrespective of treatment. Gene expression is linked to therapeutic outcome, and gene expression in the peripheral blood may be a suitable target for a prognostic test.
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