Molecular subsets in the gene expression signatures of scleroderma skin.
Molecular subsets in the gene expression signatures of scleroderma skin.
复制标题
硬皮病皮肤的基因表达特征中的分子亚群。
DOI：
10.1371/journal.pone.0002696
复制
发表时间：
2008-07-16
期刊：
影响因子：
3.7
通讯作者：
Whitfield ML
中科院分区：
文献类型：
--
作者：
Milano A;Pendergrass SA;Sargent JL;George LK;McCalmont TH;Connolly MK;Whitfield ML
硬皮病是一种具有复杂表型的临床异质性疾病。该疾病的特征在于血管功能障碍、组织纤维化、内脏器官功能障碍和导致自身抗体产生的免疫功能障碍。我们用DNA微阵列分析了不同硬皮病亚群皮肤活检组织中基因表达的全基因组模式，这些亚群包括17例系统性硬化症（SSc）伴弥漫性硬皮病（dSSc）患者，7例SSc伴局限性硬皮病（lSSc）患者，3例硬斑病患者和6例健康对照。在总共75个微阵列杂交中分析了61个皮肤活检。分层聚类分析表明，在22对SSc患者的前臂和背部皮肤中，有17对的基因表达模式几乎相同。利用基因表达的这一特性，我们选择了一组“内在”基因，并分析了固有的数据驱动的分组。不同的基因表达模式将dSSc患者与lSSc患者分开，并且两者都很容易与正常对照区分。我们的数据显示dSSc患者中有三个不同的患者组，lSSc患者中有两个组。每个组可以通过指示增殖细胞、免疫浸润和纤维化程序的独特基因表达特征来区分。内在组具有统计学显著性（p<0.001），并且每个内在组都被映射到改良的Rodnan皮肤评分、间质性肺病、胃肠道受累、指溃疡、雷诺现象和疾病持续时间的临床协变量。我们报告了一个177基因的签名，与皮肤病的严重程度dSSc。皮肤活检的全基因组基因表达谱表明，硬皮病的异质性可以用DNA微阵列定量测量。基因表达的多样性表明硬皮病患者皮肤中存在多种不同的基因表达程序。
Scleroderma is a clinically heterogeneous disease with a complex phenotype. The disease is characterized by vascular dysfunction, tissue fibrosis, internal organ dysfunction, and immune dysfunction resulting in autoantibody production. We analyzed the genome-wide patterns of gene expression with DNA microarrays in skin biopsies from distinct scleroderma subsets including 17 patients with systemic sclerosis (SSc) with diffuse scleroderma (dSSc), 7 patients with SSc with limited scleroderma (lSSc), 3 patients with morphea, and 6 healthy controls. 61 skin biopsies were analyzed in a total of 75 microarray hybridizations. Analysis by hierarchical clustering demonstrates nearly identical patterns of gene expression in 17 out of 22 of the forearm and back skin pairs of SSc patients. Using this property of the gene expression, we selected a set of ‘intrinsic’ genes and analyzed the inherent data-driven groupings. Distinct patterns of gene expression separate patients with dSSc from those with lSSc and both are easily distinguished from normal controls. Our data show three distinct patient groups among the patients with dSSc and two groups among patients with lSSc. Each group can be distinguished by unique gene expression signatures indicative of proliferating cells, immune infiltrates and a fibrotic program. The intrinsic groups are statistically significant (p<0.001) and each has been mapped to clinical covariates of modified Rodnan skin score, interstitial lung disease, gastrointestinal involvement, digital ulcers, Raynaud's phenomenon and disease duration. We report a 177-gene signature that is associated with severity of skin disease in dSSc. Genome-wide gene expression profiling of skin biopsies demonstrates that the heterogeneity in scleroderma can be measured quantitatively with DNA microarrays. The diversity in gene expression demonstrates multiple distinct gene expression programs in the skin of patients with scleroderma.
登录
查看更多内容
影响因子：
7.3
作者：
Grieco, P;Carotenuto, A;Novellino, E
通讯作者：
Novellino, E
影响因子：
6.5
作者：
FLEISCHMAJER, R;PERLISH, JS
通讯作者：
PERLISH, JS
影响因子：
64.8
作者：
Alizadeh, AA;Eisen, MB;Staudt, LM
通讯作者：
Staudt, LM
影响因子：
64.8
作者：
KORETZKY, GA;PICUS, J;WEISS, A
通讯作者：
WEISS, A
影响因子：
--
作者：
Kojima, F;Naraba, H;Kawai, S
通讯作者：
Kawai, S