Prognostic and Predictive Value of a Malignancy-Risk Gene Signature in Early-Stage Non-Small Cell Lung Cancer
Prognostic and Predictive Value of a Malignancy-Risk Gene Signature in Early-Stage Non-Small Cell Lung Cancer
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DOI：
10.1093/jnci/djr420
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发表时间：
2011-12-01
影响因子：
10.3
通讯作者：
Cress, W. Douglas
中科院分区：
文献类型：
--
作者：
Chen, Dung-Tsa;Hsu, Ying-Lin;Cress, W. Douglas
背景恶性风险基因特征由众多增殖基因组成，已被应用于预测乳腺癌风险。我们假设恶性风险基因标签对早期非小细胞肺癌（NSCLC）患者具有预后和预测价值。方法使用Director's Challenge Consortium的大型NSCLC微阵列数据集（n = 442）和两个独立的NSCLC微阵列数据集测试恶性风险基因标签预测早期NSCLC患者总生存期（OS）的能力（对于GSE 13213和GSE 14814数据集，n分别为117和133）。通过主成分分析生成总体恶性风险评分，以确定特征的预后和预测价值。使用相互作用模型研究辅助化疗（ACT）和基因签名之间的统计学显著相互作用。结果恶性风险基因签名与NSCLC患者的OS显著相关（P <0.001）。两个独立数据集的验证表明，恶性风险评分具有预后和预测价值：在未接受ACT的患者中，恶性风险评分低的患者与恶性风险评分高的患者相比，OS增加（GSE 13212和GSE 14814数据集的P值分别为0.007和0.01），表明具有预后价值;在GSE 14814数据集中，接受ACT治疗的患者在恶性风险评分高的组中存活时间更长ACT和基因标签之间存在显著的交互作用（P = .02）。结论恶性风险基因标签与OS相关，是预后和预测指标。恶性风险基因签名可能有助于改善OS的预测，并确定那些将从ACT中获益的NSCLC患者。
Background The malignancy-risk gene signature is composed of numerous proliferative genes and has been applied to predict breast cancer risk. We hypothesized that the malignancy-risk gene signature has prognostic and predictive value for early-stage non-small cell lung cancer (NSCLC) patients.Methods The ability of the malignancy-risk gene signature to predict overall survival (OS) of early-stage NSCLC patients was tested using a large NSCLC microarray dataset from the Director's Challenge Consortium (n = 442) and two independent NSCLC microarray datasets (n = 117 and 133, for the GSE13213 and GSE14814 datasets, respectively). An overall malignancy-risk score was generated by principal component analysis to determine the prognostic and predictive value of the signature. An interaction model was used to investigate a statistically significant interaction between adjuvant chemotherapy (ACT) and the gene signature. All statistical tests were two-sided.Results The malignancy-risk gene signature was statistically significantly associated with OS (P < .001) of NSCLC patients. Validation with the two independent datasets demonstrated that the malignancy-risk score had prognostic and predictive values: Of patients who did not receive ACT, those with a low malignancy-risk score had increased OS compared with a high malignancy-risk score (P = .007 and .01 for the GSE13212 and GSE14814 datasets, respectively), indicating a prognostic value; and in the GSE14814 dataset, patients receiving ACT survived longer in the high malignancy-risk score group (P = .03), and a statistically significant interaction between ACT and the signature was observed (P = .02).Conclusions The malignancy-risk gene signature was associated with OS and was a prognostic and predictive indicator. The malignancy-risk gene signature could be useful to improve prediction of OS and to identify those NSCLC patients who will benefit from ACT.