Identifying a gene expression signature of frequent COPD exacerbations in peripheral blood using network methods.
Identifying a gene expression signature of frequent COPD exacerbations in peripheral blood using network methods.
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DOI：
10.1186/s12920-014-0072-y
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发表时间：
2015-01-13
影响因子：
2.7
通讯作者：
Hersh CP
中科院分区：
文献类型：
--
作者：
Morrow JD;Qiu W;Chhabra D;Rennard SI;Belloni P;Belousov A;Pillai SG;Hersh CP
慢性阻塞性肺疾病 (COPD) 的恶化以症状急性恶化为特征，可能是由于细菌或病毒感染、环境暴露或未知因素造成的。急性加重频率可能是 COPD 患者的一个稳定特征，这可能意味着遗传易感性。观察具有不同恶化易感性的 COPD 患者上调和下调的基因、网络和通路将有助于阐明 COPD 恶化的分子特征和发病机制。基因表达阵列和血浆生物标志物数据是使用参加伽玛选择性视黄醇激动剂治疗肺气肿（TESRA）研究的受试者的全血样本获得的。使用线性回归、加权基因共表达网络分析（WGCNA）和路径分析来识别与前一年内恶化次数相关的特征和网络子模块；还研究了其他与慢性阻塞性肺病相关的表型。未发现单个基因与恶化次数显着相关。然而，使用网络方法，发现了一个具有统计学意义的基因模块，以及其他显示出中等关联的模块。使用通路分析在这些模块中观察到不同的特征，其特征是 B 细胞和 NK 细胞活性以及病毒感染的细胞标记物的差异。在两个模块中，基因集富集分析概括了两个基因表达实验的分子特征；一种涉及哮喘恶化产生的痰，另一种涉及病毒性肺部感染。血浆生物标志物髓过氧化物酶（MPO）与近期病情加重的次数相关。慢性阻塞性肺病恶化的明显特征可以在急性疾病发生后几个月的外周血中观察到。虽然在横断面分析中不能进行预测，但这些结果将有助于揭示 COPD 恶化的分子发病机制。本文的在线版本 (doi:10.1186/s12920-014-0072-y) 包含补充材料，可供授权用户使用。
Exacerbations of chronic obstructive pulmonary disease (COPD), characterized by acute deterioration in symptoms, may be due to bacterial or viral infections, environmental exposures, or unknown factors. Exacerbation frequency may be a stable trait in COPD patients, which could imply genetic susceptibility. Observing the genes, networks, and pathways that are up- and down-regulated in COPD patients with differing susceptibility to exacerbations will help to elucidate the molecular signature and pathogenesis of COPD exacerbations. Gene expression array and plasma biomarker data were obtained using whole-blood samples from subjects enrolled in the Treatment of Emphysema With a Gamma-Selective Retinoid Agonist (TESRA) study. Linear regression, weighted gene co-expression network analysis (WGCNA), and pathway analysis were used to identify signatures and network sub-modules associated with the number of exacerbations within the previous year; other COPD-related phenotypes were also investigated. Individual genes were not found to be significantly associated with the number of exacerbations. However using network methods, a statistically significant gene module was identified, along with other modules showing moderate association. A diverse signature was observed across these modules using pathway analysis, marked by differences in B cell and NK cell activity, as well as cellular markers of viral infection. Within two modules, gene set enrichment analysis recapitulated the molecular signatures of two gene expression experiments; one involving sputum from asthma exacerbations and another involving viral lung infections. The plasma biomarker myeloperoxidase (MPO) was associated with the number of recent exacerbations. A distinct signature of COPD exacerbations may be observed in peripheral blood months following the acute illness. While not predictive in this cross-sectional analysis, these results will be useful in uncovering the molecular pathogenesis of COPD exacerbations. The online version of this article (doi:10.1186/s12920-014-0072-y) contains supplementary material, which is available to authorized users.
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影响因子：
5.4
作者：
Ioannidis, Ioannis;McNally, Beth;Flano, Emilio
通讯作者：
Flano, Emilio
影响因子：
2.7
作者：
Haas BE;Horvath S;Pietiläinen KH;Cantor RM;Nikkola E;Weissglas-Volkov D;Rissanen A;Civelek M;Cruz-Bautista I;Riba L;Kuusisto J;Kaprio J;Tusie-Luna T;Laakso M;Aguilar-Salinas CA;Pajukanta P
通讯作者：
Pajukanta P
影响因子：
1.8
作者：
Feng G;Du P;Krett NL;Tessel M;Rosen S;Kibbe WA;Lin SM
通讯作者：
Lin SM
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
影响因子：
3.7
作者：
Poliska, Szilard;Csanky, Eszter;Nagy, Laszlo
通讯作者：
Nagy, Laszlo