The peripheral blood transcriptome identifies the presence and extent of disease in idiopathic pulmonary fibrosis.
The peripheral blood transcriptome identifies the presence and extent of disease in idiopathic pulmonary fibrosis.
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DOI：
10.1371/journal.pone.0037708
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Steele MP
中科院分区：
文献类型：
--
作者：
Yang IV;Luna LG;Cotter J;Talbert J;Leach SM;Kidd R;Turner J;Kummer N;Kervitsky D;Brown KK;Boon K;Schwarz MI;Schwartz DA;Steele MP
需要外周血生物标志物来识别和确定特发性肺纤维化（IPF）的程度。目前的生理学和影像学预后指标在疾病过程中诊断IPF太晚。我们假设外周血生物标志物将在疾病的早期阶段识别疾病，并促进疾病进展的监测。在Agilent微阵列上收集来自130名IPF患者的外周血RNA的基因表达谱。利用具有1%的错误发现率（FDR）的微阵列显著性分析（SAM）来鉴定在基于预测的DLCO和FVC百分比分类的样品中差异表达的基因。在1%FDR下，与对照相比，1428个基因在轻度IPF（DLCO >65%）中差异表达，并且与对照相比，2790个转录物在重度IPF（DLCO >35%）中差异表达。当按预测DLCO百分比分类时，SAM在轻度和重度IPF之间显示出13种差异表达的转录物（<5%FDR）。这些基因包括CAMP、CEACAM6、CTSG、DEFA3和A4、OLFM 4、HLTF、PACSIN 1、GABBR 1、IGHM和3个未知基因。进行了主成分分析（PCA），以确定基于疾病严重程度的离群值，并证明1例轻度病例在临床上被错误分类为重度IPF病例。当按FVC预测值百分比分类时，在轻度和重度IPF之间未发现差异表达的转录本。这些结果表明，外周血转录组有可能区分正常个体与IPF患者，以及当样本按预测DLCO百分比而非FVC分类时的疾病程度。
Peripheral blood biomarkers are needed to identify and determine the extent of idiopathic pulmonary fibrosis (IPF). Current physiologic and radiographic prognostic indicators diagnose IPF too late in the course of disease. We hypothesize that peripheral blood biomarkers will identify disease in its early stages, and facilitate monitoring for disease progression. Gene expression profiles of peripheral blood RNA from 130 IPF patients were collected on Agilent microarrays. Significance analysis of microarrays (SAM) with a false discovery rate (FDR) of 1% was utilized to identify genes that were differentially-expressed in samples categorized based on percent predicted DLCO and FVC. At 1% FDR, 1428 genes were differentially-expressed in mild IPF (DLCO >65%) compared to controls and 2790 transcripts were differentially- expressed in severe IPF (DLCO >35%) compared to controls. When categorized by percent predicted DLCO, SAM demonstrated 13 differentially-expressed transcripts between mild and severe IPF (< 5% FDR). These include CAMP, CEACAM6, CTSG, DEFA3 and A4, OLFM4, HLTF, PACSIN1, GABBR1, IGHM, and 3 unknown genes. Principal component analysis (PCA) was performed to determine outliers based on severity of disease, and demonstrated 1 mild case to be clinically misclassified as a severe case of IPF. No differentially-expressed transcripts were identified between mild and severe IPF when categorized by percent predicted FVC. These results demonstrate that the peripheral blood transcriptome has the potential to distinguish normal individuals from patients with IPF, as well as extent of disease when samples were classified by percent predicted DLCO, but not FVC.
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影响因子：
7
作者：
Heid, CA;Stevens, J;Williams, PM
通讯作者：
Williams, PM
DOI：
10.1111/j.1742-4658.2009.07370.x
发表时间：
2009-11
期刊：
The FEBS journal
影响因子：
--
作者：
Han W;Wang W;Mohammed KA;Su Y
通讯作者：
Su Y
DOI：
10.1097/spc.0b013e3282ff6336
发表时间：
2008-06-01
影响因子：
2.1
作者：
Collard, Harold R;Pantilat, Steven Z
通讯作者：
Pantilat, Steven Z
影响因子：
168.9
作者：
Noble, Paul W.;Albera, Carlo;du Bois, Roland M.
通讯作者：
du Bois, Roland M.
DOI：
10.1164/rccm.200810-1596oc
发表时间：
2009-07-15
影响因子：
24.7
作者：
Konishi, Kazuhisa;Gibson, Kevin F.;Kaminski, Naftali
通讯作者：
Kaminski, Naftali