Early2 factor (E2F) deregulation is a prognostic and predictive biomarker in lung adenocarcinoma.
Early2 factor (E2F) deregulation is a prognostic and predictive biomarker in lung adenocarcinoma.
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DOI：
10.18632/oncotarget.12672
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发表时间：
2016-12-13
期刊：
影响因子：
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通讯作者：
Cress WD
中科院分区：
文献类型：
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作者：
Chen L;Kurtyka CA;Welsh EA;Rivera JI;Engel BE;Muñoz-Antonia T;Yoder SJ;Eschrich SA;Creelan BC;Chiappori AA;Gray JE;Ramirez JL;Rosell R;Schabath MB;Haura EB;Chen DT;Cress WD
临床医生通常为切除的非小细胞肺癌患者开具辅助化疗（ACT）。然而，ACT仅将I-III期非小细胞肺癌的五年无病生存率提高了5- 15%，大多数患者没有获益。在此，E2 F途径的失调被探索作为肺腺癌患者的生物标志物。基于74个E2 F调节基因的E2 F途径评分系统针对来自两个平台的RNA进行训练：新鲜冷冻（FF）或福尔马林固定石蜡包埋（FFPE）组织。在5个基于FF的队列和2个基于FFPE的队列中测试E2 F评分作为预后生物标志物。E2 F评分在两项随机临床试验中作为预测生物标志物进行了测试; JBR 10和NATCH（新辅助紫杉醇-卡铂希望）试验。在检查的所有7个数据集中，E2 F评分在未治疗患者中是预后性的（p < 0.05）。联合队列的分期特异性分析表明，E2 F评分在I期患者中具有预后意义（p = 0.0495至<0.001;风险比HR =2.04- 2.22），在其他分期中具有相似的趋势。E2 F评分在两项联合随机临床试验的II期患者中具有强预测性，具有显著的治疗效果差异（p = 0.015）。具体而言，ACT改善了高E2 F的II期患者的生存率（p = 0.01; HR= 0.21）。5年生存率从18%提高到81%。相反，在低E2 F患者中，未经治疗的患者5年生存率为57%，ACT治疗患者为41%，HR为1.55（p = 0.47）。总之，E2 F评分为I期肺腺癌患者提供了有价值的预后信息，为II期肺腺癌患者提供了预测信息，应进一步探索其作为治疗决策支持工具。
Clinicians routinely prescribe adjuvant chemotherapy (ACT) for resected non-small cell lung cancer patients. However, ACT only improves five-year disease-free survival in stage I-III non-small cell lung cancer by 5-15%, with most patients deriving no benefit. Herein, deregulation of the E2F pathway was explored as a biomarker in lung adenocarcinoma patients. An E2F pathway scoring system, based on 74 E2F-regulated genes, was trained for RNA from two platforms: fresh-frozen (FF) or formalin-fixed paraffin-embedded (FFPE) tissues. The E2F score was tested as a prognostic biomarker in five FF-based cohorts and two FFPE-based cohorts. The E2F score was tested as a predictive biomarker in two randomized clinical trials; JBR10 and the NATCH (Neo-Adjuvant Taxol-Carboplatin Hope) trial. The E2F score was prognostic in untreated patients in all seven datasets examined (p < 0.05). Stage-specific analysis of combined cohorts demonstrated that the E2F score was prognostic in stage I patients (p = 0.0495 to <0.001; hazard ratio, HR, =2.04- 2.22) with a similar trend in other stages. The E2F score was strongly predictive in stage II patients from the two combined randomized clinical trials with a significant differential treatment effect (p = 0.015). Specifically, ACT improved survival in stage II patients with high E2F (p = 0.01; HR= 0.21). The 5-year survival increased from 18% to 81%. In contrast, in patients with low E2F, 5-year survival was 57% in untreated patients and 41% in ACT-treated patients with a HR of 1.55 (p = 0.47). In summary, the E2F score provides valuable prognostic information for Stage I and predictive information for Stage II lung adenocarcinoma patients and should be further explored as a decision support tool for their treatment.