Abstract 2354: An E2F signature predicts benefit of adjuvant chemotherapy in early-stage non-small cell lung cancer.

Abstract

Early-stage non-small cell lung cancer (NSCLC) is primarily treated by surgical resection. Unfortunately, after resection, one-third to one-half of early-stage patients will die of metastatic recurrence. Adjuvant chemotherapy (ACT) improves the survival of patients with early-stage disease and has become the standard treatment for patients with resected stage II-III NSCLC. However, the five-year survival advantage of ACT is only 4%-15% suggesting that many patients do not benefit. Given the morbidity associated with ACT, it is imperative to develop new prognostic tools to identify those patients with a high probability of relapse. Toward this end, we have used small inhibitory RNAs targeting multiple E2F pathway components to derive an E2F gene expression signature in vitro. This signature was refined by filtering for its components that were altered in non-small cell lung cancers compared to normal tissue. Principle component analysis was then used to represent the signature which was tested for correlation to overall survival in two large cohorts. The first of the two cohorts was the Molecular Classification of Lung Adenocarcinoma (MCLA) from the Director's Challenge Consortium and the second was a novel database on 444 lung adenocarcinomas treated as a part of Moffitt's Total Cancer Care Network. The E2F signature is strongly prognostic in both cohorts with P values <0.0001. Additionally, using data in the JBR.10 trial (GSE14814) for patients who either did or did not receive ACT we were able to determine that patients having a high E2F signature benefit from ACT (have increased overall survival), whereas patients with a low E2F signature do not. Overall, these results suggest that this approach could be optimized in the clinical setting to distinguish patients likely to benefit from ACT from those who will not. Citation Format: Courtney A. Kurtyka, Dung-Tsa Chen, Lu Chen, William Brazelle, Eric A. Welsh, Anders E. Berglund, Steven A. Eschrich, Matthew B. Schabath, Eric B. Haura, W. Douglas Cress. An E2F signature predicts benefit of adjuvant chemotherapy in early-stage non-small cell lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2354. doi:10.1158/1538-7445.AM2013-2354