A multigene assay is prognostic of survival in patients with early-stage lung adenocarcinoma
A multigene assay is prognostic of survival in patients with early-stage lung adenocarcinoma
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DOI：
10.1158/1078-0432.ccr-08-0544
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发表时间：
2008-09-01
影响因子：
11.5
通讯作者：
Jablons, David M.
中科院分区：
文献类型：
--
作者：
Raz, Dan J.;Ray, M. Roshni;Jablons, David M.
目的：临床分期不足以对早期非小细胞肺癌患者进行危险分层。我们试图建立一个基于实时定量聚合酶链式反应(RT-PCR)的早期肺腺癌患者的预后模型。实验设计：我们使用RT-PCR技术研究了107例完全手术切除的肺腺癌患者中61个候选基因的表达。我们使用交叉验证方法来选择和验证基于有限数量基因表达的预后模型。结果：建立了基于Wnt3a、ERBB3、LCK和RND3表达的四基因模型。风险评分对死亡率的预测优于临床分期或肿瘤大小(调整后的风险比为6.7；95%可信区间为1.6-28.9；P=0.001)。在70例I期患者中，低风险评分患者的5年总生存率为87%，高风险评分患者的5年总生存率为38%(P=0.0002)。在所有患者中，5年总生存率分别为62%和41%(P0054)。低风险评分患者和高风险评分患者之间的无病生存率也有显著差异。结论：这种多基因检测方法对早期肺腺癌患者的总体和无病生存率的预测明显优于临床分期和肿瘤大小，尤其是在I期疾病患者中表现更好。需要进行前瞻性临床试验，以确定I期疾病的高危患者是否从辅助化疗中受益。
Purpose: Clinical staging does not adequately risk stratify patients with early stage non-small cell lung cancer. We sought to generate a real-time PCR (RT-PCR) -based prognostic model in patients with early stage lung adenocarcinoma, the dominant histology of lung cancer in the United States.Experimental Design: We studied gene expression of 61 candidate genes in 107 patients with completely surgically resected lung adenocarcinoma using RT-PCR. We used crossvalidation methods to select and validate a prognostic model based on the expression of a limited number of genes. A risk score was generated based on model coefficients, and survival of patients with high- and low-risk scores were analyzed.Results: We generated a four-gene model based on expression of WNT3a, ERBB3, LCK, and RND3. Risk score predicted mortality better than clinical stage or tumor size (adjusted hazard ratio, 6.7; 95% confidence interval, 1.6-28.9; P = 0.001). Among 70 patients with stage I disease, 5-year overall survival was 87% among patients with low-risk scores, and 38% among patients with high-risk scores (P = 0.0002). Among all patients, 5-year overall survival was 62% and 41%, respectively (P 0,0054). Disease-free survival was also significantly different among low- and high-risk score patients.Conclusions: This multigene assay predicts overall and disease-free survival significantly better than clinical stage and tumor size in patients with early stage lung adenocarcinorna and performs especially well in patients with stage I disease. Prospective clinical trials are needed to determine whether high-risk patients with stage I disease benefit from adjuvant chemotherapy.