ChipDX LLC, PO Box 286874, New York, NY 10128, USA.
BMC Med Genomics. 2012 Jul 2;5:30. doi: 10.1186/1755-8794-5-30.
Improved methods are needed for predicting prognosis and the benefit of delivering adjuvant chemotherapy (ACT) in patients with non-small-cell lung cancer (NSCLC).
A novel prognostic algorithm was identified using genomic profiles from 332 stage I-III adenocarcinomas and independently validated on a separate series of 264 patients with stage I-II tumors, compiled from five previous studies. The prognostic algorithm was used to interrogate genomic data from a series of patients treated with adjuvant chemotherapy. Those genes associated with outcome in the adjuvant treatment setting, independent to prognosis were used to train an algorithm able to classify a patient as either a responder or non-responder to ACT. The performance of this signature was independently validated on a separate series of genomic profiles from patients enrolled in a randomized controlled trial of cisplatin/vinorelbine vs. observation alone (JBR.10).
NSCLC patients exhibiting the high-risk, poor-prognosis form of the 160-gene prognosis signature experienced a 2.80-times higher rate of 5-year disease specific death (log rank P < 0.0001) compared to those with the low-risk, good prognosis profile, adjusted for covariates. The prognosis signature was found to especially accurate at identifying early stage patients at risk of disease specific death within 24 months of diagnosis when compared to traditional methods of outcome prediction.Separately, NSCLC patients with the 37-gene ACT-response signature (n = 70, 64 %), benefited significantly from cisplatin/vinorelbine (adjusted HR: 0.23, P = 0.0032). For those patients predicted to be responders, receiving this form of ACT conferred a 25 % improvement in the probability of 5-year-survival, compared to observation alone and adjusted for covariates. Conversely, in those patients predicted to be non-responders, ACT was observed to offer no significant survival benefit (adjusted HR: 0.55, P = 0.32).The two gene signatures overlap by one gene only SPSB3, which interacts with the oncogene MET. In this study, higher levels of SPSB3 which were associated with favorable prognosis and benefit from ACT.
These complimentary prognostic and predictive gene signatures may assist physicians in their management and treatment of patients with early stage lung cancer.
需要改进方法来预测非小细胞肺癌 (NSCLC) 患者的预后和辅助化疗 (ACT) 的获益。
使用来自 332 例 I-III 期腺癌患者的基因组谱识别了一种新的预后算法，并在来自五个先前研究的 264 例 I-II 期肿瘤患者的独立系列中进行了验证。该预后算法用于分析接受辅助化疗的一系列患者的基因组数据。那些在辅助治疗环境中与结局相关且与预后无关的基因，被用于训练一种能够将患者分类为对 ACT 有反应或无反应的算法。该特征的性能在接受顺铂/长春瑞滨与单独观察的随机对照试验 (JBR.10) 中入组的患者的基因组谱的单独系列中进行了独立验证。
与具有低风险、预后良好特征的患者相比，表现出 160 个基因预后特征的高危、预后不良的 NSCLC 患者，5 年疾病特异性死亡的发生率高 2.80 倍（对数秩 P<0.0001），调整了协变量。与传统的预后预测方法相比，该预后特征在识别诊断后 24 个月内有疾病特异性死亡风险的早期患者时尤其准确。另外，具有 37 个 ACT 反应基因特征的 NSCLC 患者（n=70，64%）从顺铂/长春瑞滨中显著获益（调整后的 HR：0.23，P=0.0032）。对于那些预测为有反应的患者，与单独观察并调整协变量相比，接受这种形式的 ACT 可使 5 年生存率提高 25%。相反，对于那些预测为无反应的患者，ACT 并未观察到显著的生存获益（调整后的 HR：0.55，P=0.32）。两个基因特征仅重叠一个基因 SPSB3，该基因与致癌基因 MET 相互作用。在这项研究中，SPSB3 水平较高与预后良好和 ACT 获益相关。
这些互补的预后和预测基因特征可帮助医生管理和治疗早期肺癌患者。
