An Immune Response Enriched 72-Gene Prognostic Profile for Early-Stage Non-Small-Cell Lung Cancer
An Immune Response Enriched 72-Gene Prognostic Profile for Early-Stage Non-Small-Cell Lung Cancer
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DOI：
10.1158/1078-0432.ccr-08-1258
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发表时间：
2009-01-01
影响因子：
11.5
通讯作者：
van Zandwijk, Nico
中科院分区：
文献类型：
--
作者：
Roepman, Paul;Jassem, Jacek;van Zandwijk, Nico
目的：目前的分期方法对早期非小细胞肺癌（NSCLC）的预后预测不准确。我们的目标是建立I期和II期NSCLC的基因表达谱，以便在初始诊断后2至3年内识别疾病复发风险高的患者。实验设计：我们使用全基因组基因表达微阵列分析了来自5个欧洲机构的172例非小细胞肺癌患者（pT1-2, N0-1, M0）的冷冻肿瘤样本，这些患者接受了完全的手术切除。中位随访89个月（范围1.2-389），64例患者复发。随机三分之二的样本被分配为训练队列，其余样本留作独立验证。Cox比例风险模型用于评估个体基因表达水平与患者无复发生存之间的关系。采用最接近均值分析来开发疾病复发的基因表达分类器。结果：我们开发了一个72基因表达预后的NSCLC分类器。根据分类器评分，将患者分为疾病复发风险高或低两类。低危患者在训练组（P < 0.001, n = 103）和独立验证组（P < 0.01, n = 69）的无复发生存率均显著提高。在我们的预后标记中，与免疫反应相关的基因被强烈富集。结论：我们的72基因标记与早期NSCLC患者的无复发和总生存率密切相关，可能成为患者选择辅助治疗的工具。
Purpose: Current staging methods are imprecise for predicting prognosis of early-stage non small-cell lung cancer (NSCLC). We aimed to develop a gene expression profile for stage I and stage II NSCLC, allowing identification of patients with a high risk of disease recurrence within 2 to 3 years after initial diagnosis.Experimental Design: We used whole-genome gene expression microarrays to analyze frozen tumor samples from 172 NSCLC patients (pT1-2, N0-1, M0) from five European institutions, who had undergone complete surgical resection. Median follow-up was 89 months (range, 1.2-389) and 64 patients developed a recurrence. A random two thirds of the samples were assigned as the training cohort with the remaining samples set aside for independent validation. Cox proportional hazards models were used to evaluate the association between expression levels of individual genes and patient recurrence-free survival. A nearest mean analysis was used to develop a gene-expression classifier for disease recurrence.Results: We have developed a 72-gene expression prognostic NSCLC classifier. Based on the classifier score, patients were classified as either high or low risk of disease recurrence. Patients classified as low risk showed a significantly better recurrence-free survival both in the training set (P < 0.001; n = 103) and in the independent validation set (P < 0.01; n = 69). Genes in our prognostic signature were strongly enriched for genes associated with immune response.Conclusions: Our 72-gene signature is closely associated with recurrence-free and overall survival in early-stage NSCLC patients and may become a tool for patient selection for adjuvant therapy.