Comprehensive gene expression profiling identifies distinct and overlapping transcriptional profiles in non-specific interstitial pneumonia and idiopathic pulmonary fibrosis.
Comprehensive gene expression profiling identifies distinct and overlapping transcriptional profiles in non-specific interstitial pneumonia and idiopathic pulmonary fibrosis.
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DOI：
10.1186/s12931-018-0857-1
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发表时间：
2018-08-15
影响因子：
5.8
通讯作者：
Mura M
中科院分区：
文献类型：
--
作者：
Cecchini MJ;Hosein K;Howlett CJ;Joseph M;Mura M
特发性肺纤维化(IPF)和非特异性间质性肺炎(NSIP)之间的临床-放射学区别具有挑战性。我们试图研究IPF和NSIP与正常对照的基因表达谱。检测IPF患者(n = 22例)、NSIP10例(n = 10例)和正常对照组(n = 11例)移植肺的基因表达。基因芯片分析包括基因芯片显著性分析(SAM)、独创性路径分析、基因集富集法和非监督系统聚类法。对感兴趣的蛋白质进行免疫组织化学和血清学检测。NSIP患者中与免疫反应机制相关的基因显著丰富，如T细胞反应和白细胞向肺间室的募集。相反，在IPF中，这些涉及衰老、上皮向间充质转化、肌成纤维细胞分化和胶原沉积。与IPF组不同，NSIP病例表现出惊人的同质性基因签名。聚类分析发现，IPF患者中有一组SAM选择的基因表达中等或不明确，NSIP特异性基因和衰老相关基因都有有趣的上调。成纤维细胞上衰老标志物p16的免疫组织化学染色可区分大多数IPF和NSIP。作为一种衰老效应因子，一系列血清Periostin水平预测了一组IPF患者的临床进展。在移植肺中全面的基因表达谱确定了IPF和NSIP中不同的转录图谱和差异表达的基因，支持NSIP作为独立疾病的概念。筛选出了能区分IPF和NSIP的潜在基因和蛋白质标记，其中衰老在IPF中的作用最为显著。一组同时具有NSIP和衰老转录特征的IPF患者的发现提出了一种假设，即“衰老的”NSIP可能是发生重叠IPF的危险因素。本文的在线版本(10.1186/s12931-0180857-1)包含向授权用户提供的补充材料。
The clinical-radiographic distinction between idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP) is challenging. We sought to investigate the gene expression profiles of IPF and NSIP vs. normal controls. Gene expression from explanted lungs of patients with IPF (n = 22), NSIP (n = 10) and from normal controls (n = 11) was assessed. Microarray analysis included Significance Analysis of Microarray (SAM), Ingenuity Pathway, Gene-Set Enrichment and unsupervised hierarchical clustering analyses. Immunohistochemistry and serology of proteins of interest were conducted. NSIP cases were significantly enriched for genes related to mechanisms of immune reaction, such as T-cell response and recruitment of leukocytes into the lung compartment. In IPF, in contrast, these involved senescence, epithelial-to-mesenchymal transition, myofibroblast differentiation and collagen deposition. Unlike the IPF group, NSIP cases exhibited a strikingly homogenous gene signature. Clustering analysis identified a subgroup of IPF patients with intermediate and ambiguous expression of SAM-selected genes, with the interesting upregulation of both NSIP-specific and senescence-related genes. Immunohistochemistry for p16, a senescence marker, on fibroblasts differentiated most IPF cases from NSIP. Serial serum levels of periostin, a senescence effector, predicted clinical progression in a cohort of patients with IPF. Comprehensive gene expression profiling in explanted lungs identifies distinct transcriptional profiles and differentially expressed genes in IPF and NSIP, supporting the notion of NSIP as a standalone condition. Potential gene and protein markers to discriminate IPF from NSIP were identified, with a prominent role of senescence in IPF. The finding of a subgroup of IPF patients with transcriptional features of both NSIP and senescence raises the hypothesis that “senescent” NSIP may represent a risk factor to develop superimposed IPF. The online version of this article (10.1186/s12931-018-0857-1) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Ohta S;Okamoto M;Fujimoto K;Sakamoto N;Takahashi K;Yamamoto H;Kushima H;Ishii H;Akasaka K;Ono J;Kamei A;Azuma Y;Matsumoto H;Yamaguchi Y;Aihara M;Johkoh T;Kawaguchi A;Ichiki M;Sagara H;Kadota JI;Hanaoka M;Hayashi SI;Kohno S;Hoshino T;Izuhara K;Consortium for Development of Diagnostics for Pulmonary Fibrosis Patients (CoDD-PF)
通讯作者：
Consortium for Development of Diagnostics for Pulmonary Fibrosis Patients (CoDD-PF)
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
DOI：
10.1164/ajrccm.164.9.2103074
发表时间：
2001-11-01
影响因子：
24.7
作者：
Flaherty, KR;Travis, WD;Martinez, FJ
通讯作者：
Martinez, FJ
影响因子：
9.6
作者：
Huh, Jin Won;Kim, Dong Soon;Kim, Kyu Rae
通讯作者：
Kim, Kyu Rae
DOI：
10.1164/rccm.200402-147oc
发表时间：
2004-10-15
影响因子：
24.7
作者：
Flaherty, KR;King, TE;Martinez, FJ
通讯作者：
Martinez, FJ