Intrinsic gene expression subsets of diffuse cutaneous systemic sclerosis are stable in serial skin biopsies.
Intrinsic gene expression subsets of diffuse cutaneous systemic sclerosis are stable in serial skin biopsies.
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DOI：
10.1038/jid.2011.472
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发表时间：
2012-05
影响因子：
6.5
通讯作者：
Whitfield, Michael L.
中科院分区：
文献类型：
--
作者：
Pendergrass, Sarah A.;Lemaire, Raphael;Francis, Ian P.;Mahoney, J. Matthew;Lafyatis, Robert;Whitfield, Michael L.
通过 DNA 微阵列分析了参加利妥昔单抗开放标签研究的 13 名 dSSc 患者、9 名未接受利妥昔单抗治疗的 dSSc 患者和 9 名健康对照者的皮肤活检基因表达。这些数据概括了之前描述的患者“内在”基因表达子集，包括增殖、炎症和正常样组。连续皮肤活检显示随着时间的推移，基因表达是一致且非进展的，重要的是，炎症亚组的患者不会转移到纤维增殖亚组，反之亦然。我们无法检测到利妥昔单抗治疗前后基因表达的显着差异，这与明显缺乏临床反应相一致。无论治疗方案或采集时间点如何，每位患者的连续活检都保持在相同的基因表达子集中。总的来说，这些数据强调了 SSc 的异质性，并证明内在子集是疾病固有的、可重复的和稳定的特征，与病程无关。此外，这些数据对于 SSc 个性化治疗的未来发展具有根本重要性；针对炎症的药物可能会使那些具有炎症特征的患者受益，而针对纤维化的药物可能会使那些具有纤维增殖特征的患者受益。
Skin biopsy gene expression was analyzed by DNA microarray from 13 dSSc patients enrolled in an open label study of rituximab, 9 dSSc patients not treated with rituximab, and 9 healthy controls. These data recapitulate the patient ‘intrinsic’ gene expression subsets described previously including proliferation, inflammatory, and normal-like groups. Serial skin biopsies showed consistent and non-progressing gene expression over time, and importantly, the patients in the inflammatory subset do not move to the fibroproliferative subset, and vice versa. We were unable to detect significant differences in gene expression before and after rituximab treatment, consistent with an apparent lack of clinical response. Serial biopsies from each patient stayed within the same gene expression subset regardless of treatment regimen or the time point at which they were taken. Collectively, these data emphasize the heterogeneous nature of SSc and demonstrate that the intrinsic subsets are an inherent, reproducible and stable feature of the disease that is independent of disease duration. Moreover, these data have fundamental importance for the future development of personalized therapy for SSc; drugs targeting inflammation are likely to benefit those patients with an inflammatory signature, whereas drugs targeting fibrosis are likely to benefit those with a fibroproliferative signature.
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影响因子：
5
作者：
KRALING, BM;MAUL, GG;JIMENEZ, SA
通讯作者：
JIMENEZ, SA
影响因子：
5.8
作者：
Benito, M;Parker, J;Marron, JS
通讯作者：
Marron, JS
David Gene功能分类工具：一种以生物模块为中心的新型算法，可在功能上分析大基因列表。
影响因子：
12.3
作者：
Huang, Da Wei;Sherman, Brad T;Tan, Qina;Collins, Jack R;Alvord, W Gregory;Roayaei, Jean;Stephens, Robert;Baseler, Michael W;Lane, H Clifford;Lempicki, Richard A
通讯作者：
Lempicki, Richard A
硬皮病皮肤的基因表达特征中的分子亚群。
影响因子：
3.7
作者：
Milano A;Pendergrass SA;Sargent JL;George LK;McCalmont TH;Connolly MK;Whitfield ML
通讯作者：
Whitfield ML
影响因子：
3.7
作者：
Pendergrass SA;Hayes E;Farina G;Lemaire R;Farber HW;Whitfield ML;Lafyatis R
通讯作者：
Lafyatis R