Transcriptional Profiles Predict Disease Outcome in Patients with Cutaneous T-Cell Lymphoma
Transcriptional Profiles Predict Disease Outcome in Patients with Cutaneous T-Cell Lymphoma
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DOI：
10.1158/1078-0432.ccr-09-2879
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发表时间：
2010-04-01
影响因子：
11.5
通讯作者：
Kupper, Thomas S.
中科院分区：
文献类型：
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作者：
Litvinov, Ivan V.;Jones, David A.;Kupper, Thomas S.
目的：皮肤t细胞淋巴瘤（CTCL）的平均生存与诊断时的临床分期有关，其中I期有良好的生存预后，而更晚期的患者在5年内死于疾病。虽然大多数患者表现为早期CTCL，但其中15%至20%的患者不可避免地会进展。目前最先进的临床标准不能识别有进展风险的I期疾病个体。当前工作的目的是获得新的分子洞察CTCL的病理生理，以便能够识别预后不良和良好的患者。我们之前的工作使用微阵列分析来自62名CTCL患者的皮肤活检，对基因表达进行无监督分析，揭示了三种不同的转录谱簇。实验设计：在本研究中，我们使用逆转录- pcr来确认每个集群中代表性基因子集的基因表达水平。我们还在6年临床随访的基础上进行了生存和疾病进展的Kaplan-Meier分析。结果：我们的逆转录- pcr结果证实了每个聚类的代表性基因上调，而临床分析表明，所有进展到II期及以上的I期病例都属于预后差和中预后1和3类，没有一例预后良好2类。该分析还确定了在预后良好（如WIF-1）和预后不良（如IL-17F）集群中优先表达的某些基因。结论：本研究提示根据基因表达将CTCL患者分为低危、中危和高危三组是可能的。临床癌症研究；16 (7);2106 - 14所示。AACR (C) 2010。
Purpose: Average survival of cutaneous T-cell lymphoma (CTCL) is associated with clinical stage at diagnosis, where stage I has a favorable survival prognosis, whereas patients with more advanced stages succumb to their disease within 5 years. Although the majority of patients present with an early-stage CTCL, 15% to 20% of them will inevitably progress. Current state-of-the-art clinical criteria cannot identify individuals with stage I disease who are at risk of progression. The purpose of the current work is to gain novel molecular insight into the pathophysiology of CTCL to be able to identify patients with poor versus favorable prognosis. Our previous work used microarray analysis of skin biopsies from 62 CTCL patients to perform an unsupervised analysis of gene expression, which revealed three distinct transcription profile clusters.Experimental Design: In the present study, we used reverse transcription-PCR to confirm gene expression levels for a subset of representative genes in each cluster. We also performed a Kaplan-Meier analysis of survival and disease progression based on the 6 years of clinical follow-up.Results: Our reverse transcription-PCR results confirmed the upregulation of representative genes for each cluster, whereas clinical analysis documents that all stage I cases that progressed to stage II and beyond were in poor and intermediate prognosis clusters 1 and 3 and none were in favorable prognosis cluster 2. This analysis also identified certain genes that were preferentially expressed in favorable (e. g., WIF-1) versus poor (e. g., IL-17F) prognosis clusters.Conclusion: This work suggests that it may be possible to stratify CTCL patients into low-risk, intermediate-risk, and high-risk groups based on gene expression. Clin Cancer Res; 16(7); 2106-14. (C)2010 AACR.