期刊
ONCOTARGET
卷 7, 期 50, 页码 82254-82265出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.12672
关键词
lung adenocarcinoma; adjuvant chemotherapy; E2F; predictive biomarker; prognostic biomarker
资金
- La Caixa Foundation
- Redes Tematicas en Cancer (RTICC) [RD12/0036/0072]
- James and Esther King Biomedical Research Program Grant from the Florida Department of Health [5JK06]
- National Institutes of Health/National Cancer Institute grant [CA90489]
- Specialized Programs of Research Excellence (SPORE) [P50 CA119997]
- U54 Partnership Grant [CA163068]
- USF Presidential Fellowship
- Moffitt's Lung Cancer Center of Excellence
- Tissue Core and Molecular Genomics Facilities at the H. Lee Moffitt Cancer Center & Research Institute, an NCI-designated Comprehensive Cancer Center [P30-CA076292]
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.
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