Lesional gene expression profiling in cutaneous T-cell lymphoma reveals natural clusters associated with disease outcome
Lesional gene expression profiling in cutaneous T-cell lymphoma reveals natural clusters associated with disease outcome
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DOI：
10.1182/blood-2006-12-061507
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发表时间：
2007-10-15
期刊：
影响因子：
20.3
通讯作者：
Kupper, Thomas S.
中科院分区：
文献类型：
--
作者：
Shin, Jessica;Monti, Stefano;Kupper, Thomas S.
皮肤T细胞淋巴瘤（CTCL）的定义是激活和恶性T细胞浸润在皮肤。CTCL的临床表现和预后变化很大。在这项研究中，我们假设在病变皮肤活检中的基因表达分析可以提高对疾病及其治疗的理解。基于63份皮肤样本，我们进行了共识聚类，揭示了3个患者聚类。其中，2组倾向于区分有限CTCL （IA期和IB期）和更广泛的CTCL （IB期和III期）。IB期患者在两组中均有出现，但有限CTCL组患者对治疗的反应比更广泛CTCL组患者更敏感。第三簇富含淋巴细胞激活基因，与高比例的肿瘤（IIB期）病变相关。生存分析显示各组间无事件生存率存在显著差异，活化淋巴细胞组生存率最低。通过监督分析，我们进一步表征了与低阶段/治疗反应性CTCL和高阶段/治疗抵抗性CTCL显著相关的基因。我们的结论是，CTCL皮肤病变的转录谱揭示了临床相关的特征，与生存和治疗反应的差异相关。进一步的前瞻性长期研究来验证和完善这些发现似乎是有必要的。
Cutaneous T-cell lymphoma (CTCL) is defined by infiltration of activated and malignant T cells in the skin. The clinical manifestations and prognosis in CTCL are highly variable. In this study, we hypothesized that gene expression analysis in lesional skin biopsies can improve understanding of the disease and its management. Based on 63 skin samples, we performed consensus clustering, revealing 3 patient clusters. Of these, 2 clusters tended to differentiate limited CTCL (stages IA and IB) from more extensive CTCL (stages IB and III). Stage IB patients appeared in both clusters, but those in the limited CTCL cluster were more responsive to treatment than those in the more extensive CTCL cluster. The third cluster was enriched in lymphocyte activation genes and was associated With a high proportion of tumor (stage IIB) lesions. Survival analysis revealed significant differences in event-free survival between clusters, with poorest survival seen in the activated lymphocyte cluster. Using supervised analysis, we further characterized genes significantly associated with lower-stage/treatment-responsive CTCL versus higher-stage/treatment-resistant CTCL. We conclude that transcriptional profiling of CTCL skin lesions reveals clinically relevant signatures, correlating with differences in survival and response to treatment. Additional prospective long-term studies to validate and refine these findings appear warranted.