Peripheral blood mononuclear cell gene expression profiles predict poor outcome in idiopathic pulmonary fibrosis.
Peripheral blood mononuclear cell gene expression profiles predict poor outcome in idiopathic pulmonary fibrosis.
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DOI：
10.1126/scitranslmed.3005964
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发表时间：
2013-10-02
影响因子：
17.1
通讯作者：
Kaminski N
中科院分区：
文献类型：
--
作者：
Herazo-Maya JD;Noth I;Duncan SR;Kim S;Ma SF;Tseng GC;Feingold E;Juan-Guardela BM;Richards TJ;Lussier Y;Huang Y;Vij R;Lindell KO;Xue J;Gibson KF;Shapiro SD;Garcia JG;Kaminski N
我们旨在通过在发现和复制IPF患者队列中对外周血单个核细胞（PBMC）进行微阵列实验，确定可预测特发性肺纤维化（IPF）不良预后的外周血单个核细胞（PBMC）基因表达谱。微阵列分析在发现队列中确定了52个与无移植生存（TFS）相关的基因。使用52基因结果预测标记对复制队列的微阵列样本进行聚类，区分两组患者在TFS方面存在显著差异。我们在每个独立的微阵列队列中研究了与TFS相关的途径，发现了“T细胞激活过程中的共刺激信号”Biocarta途径的表达减少，特别是CD28、ICOS、LCK和ITK基因的表达减少，定量逆转录聚合酶链反应（qRT-PCR）证实了这一结果。一个比例风险模型，包括CD28、ICOS、LCK和ITK的qRT-PCR表达，以及患者的年龄、性别和预测的强制肺活量百分比（FVC%），显示在2.4个月时，复制队列中死亡和肺移植预测的接受者工作特征曲线下面积为78.5%。为了评估CD28、ICOS、LCK和ITK表达的潜在细胞来源，我们分析并发现这些基因与复制队列中CD4+CD28+ T细胞的PBMC百分比存在显著相关性。我们的研究结果表明，CD28、ICOS、LCK和ITK是IPF的潜在结局生物标志物，应该进一步评估患者在肺移植中的优先级和药物研究中的分层。
We aimed to identify peripheral blood mononuclear cell (PBMC) gene expression profiles predictive of poor outcomes in idiopathic pulmonary fibrosis (IPF) by performing microarray experiments of PBMCs in discovery and replication cohorts of IPF patients. Microarray analyses identified 52 genes associated with transplant-free survival (TFS) in the discovery cohort. Clustering the microarray samples of the replication cohort using the 52-gene outcome-predictive signature distinguished two patient groups with significant differences in TFS. We studied the pathways associated with TFS in each independent microarray cohort and identified decreased expression of “The costimulatory signal during T cell activation” Biocarta pathway and, in particular, the genes CD28, ICOS, LCK, and ITK, results confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). A proportional hazards model, including the qRT-PCR expression of CD28, ICOS, LCK, and ITK along with patient’s age, gender, and percent predicted forced vital capacity (FVC%), demonstrated an area under the receiver operating characteristic curve of 78.5% at 2.4 months for death and lung transplant prediction in the replication cohort. To evaluate the potential cellular source of CD28, ICOS, LCK, and ITK expression, we analyzed and found significant correlation of these genes with the PBMC percentage of CD4+CD28+ T cells in the replication cohort. Our results suggest that CD28, ICOS, LCK, and ITK are potential outcome biomarkers in IPF and should be further evaluated for patient prioritization for lung transplantation and stratification in drug studies.
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影响因子：
3.7
作者：
Gilani SR;Vuga LJ;Lindell KO;Gibson KF;Xue J;Kaminski N;Valentine VG;Lindsay EK;George MP;Steele C;Duncan SR
通讯作者：
Duncan SR
影响因子：
14.9
作者：
Schaefer, Carl F.;Anthony, Kira;Buetow, Kenneth H.
通讯作者：
Buetow, Kenneth H.
影响因子：
14.9
作者：
Ruepp, Andreas;Brauner, Barbara;Dunger-Kaltenbach, Irmtraud;Frishman, Goar;Montrone, Corinna;Stransky, Michael;Waegele, Brigitte;Schmidt, Thorsten;Doudieu, Octave Noubibou;Mpflen, Volker Stu;Mewes, H. Werner
通讯作者：
Mewes, H. Werner
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
DOI：
10.1164/rccm.200211-1311oc
发表时间：
2003-09-01
影响因子：
24.7
作者：
Collard, HR;King, TE;Brown, KK
通讯作者：
Brown, KK