Validation of a histology-independent prognostic gene signature for early stage, non-small cell lung cancer including stage IA patients

Background: Patients with early stage non-small cell lung carcinoma (NSCLC) may benefit from treatments based on more accurate prognosis. A 15-gene prognostic classifier for NSCLC was identified from mRNA expression profiling of tumor samples from the NCIC CTG JBR.10 trial. Here, we assessed its value in an independent set of cases. Methods: Expression profiling was performed on RNA from frozen, resected tumor tissues corresponding to 181 Stage I and II NSCLC cases collected at University Health Network (UHN181). Kaplan-Meier methodology was used to estimate three year overall survival probabilities and the prognostic effect of the classifier was assessed using log-rank testing. Cox proportional hazards model evaluated the signature's effect adjusting for clinical prognostic factors. Results: Expression data of the 15-gene classifier stratified UHN181 cases into high and low-risk subgroups with significantly different overall survival (HR=1.92, 95% CI: 1.15-3.23, p=0.012). Its strength as a prognostic classifier was superior to stage alone (HR=1.52, 95% CI: 0.90-2.55, p-value=0.11). In subgroup analysis, this classifier predicted survival in 127 Stage I patients (HR=2.17, 95% CI: 1.12-4.20, p=0.018) and the smaller subgroup of 48 Stage IA patients (HR=5.61, 95% CI: 1.19-26.45, p=0.014. The signature was prognostic for both adenocarcinoma and squamous cell carcinoma cases (HR= 1.76, p-value=0.058; HR= 4.19, p-value=0.045, respectively). Conclusions: The prognostic accuracy of a 15-gene classifier was validated in an independent cohort of 181 early stage NSCLC samples including Stage IA cases and in different NSCLC histologic subtypes. Expression profiling was performed on RNA from frozen, resected tumor tissues corresponding to 181 Stage I and II NSCLC cases collected at University Health Network (UHN181). !Series_contributor = Sandy,D,Der

背景：早期非小细胞肺癌（non-small cell lung carcinoma, NSCLC）患者可从基于更精准预后评估的治疗方案中获益。研究人员从NCIC CTG JBR.10试验的肿瘤样本信使RNA（mRNA）表达谱中，筛选出一款针对非小细胞肺癌的15基因预后分类器。本研究旨在评估该分类器在独立病例队列中的应用价值。
方法：本研究对大学健康网络（University Health Network, UHN）收集的181例Ⅰ期及Ⅱ期非小细胞肺癌患者的冰冻切除肿瘤组织RNA进行了表达谱检测，该队列记为UHN181。采用Kaplan-Meier法（Kaplan-Meier）估算3年总生存率，通过log-rank检验（log-rank testing）评估该分类器的预后效应；使用Cox比例风险模型（Cox proportional hazards model）校正临床预后因素后，评估该基因标签的预后价值。
结果：15基因分类器的表达谱数据将UHN181队列划分为高、低风险两个亚组，两组总生存率存在显著差异（风险比HR=1.92，95%置信区间CI:1.15-3.23，p=0.012）。该分类器的预后效能优于单纯临床分期（HR=1.52，95%CI:0.90-2.55，p=0.11）。亚组分析显示，该分类器可对127例Ⅰ期患者的生存情况进行预测（HR=2.17，95%CI:1.12-4.20，p=0.018），也可对48例ⅠA期亚组患者进行预测（HR=5.61，95%CI:1.19-26.45，p=0.014）。该基因标签对腺癌和鳞状细胞癌患者均具有预后价值（分别对应HR=1.76，p=0.058；HR=4.19，p=0.045）。
结论：本研究在包含181例早期非小细胞肺癌样本（含ⅠA期患者）以及不同组织学亚型非小细胞肺癌患者的独立队列中，验证了15基因分类器的预后准确性。
本研究对大学健康网络收集的181例Ⅰ期及Ⅱ期非小细胞肺癌患者的冰冻切除肿瘤组织RNA进行了表达谱检测，该队列记为UHN181。
系列贡献者：Sandy,D,Der