Abstract 1993: Higher activity of cell proliferation is associated with poor survival in lung adenocarcinoma

Abstract

Abstract The number of patients with lung adenocarcinoma, a major histological type of lung cancer, has soared recently. Although some lung adenocarcinoma patients could be diagnosed at early stages and received surgical resection, nearly 50% of patients still died from recurrence. This phenomenon indicates that using only traditional prognostic factors, like TMN staging, is not sufficient for regimen decision. Here we proposed a bioinformatic method to evaluate the activity of cell cycle from expression profiles and proved that the activity of cell cycle can be applied as prognostic factor of lung adenocarcinoma, especially for early stages. A gene set named as cell cycle signature (CCS), which correlated with cell cycling, was used to measure the activity of tumor proliferation. The E2F1 target genes and E2F3 target genes were also applied to measure the E2F signaling pathway activity, which was regulated by the cell cycle. The prognostic ability of these gene sets was evaluated by applying Cox hazard proportional analysis to three microarray datasets of lung adenocarcinoma. Our result revealed that the association between high activities of cell cycle and poor survival outcomes existed in lung adenocarcinoma patients. The result of Cox hazard proportional analysis showed that the CCS and E2F1/E2F3 target genes are significant contributors to survival risk. The p-values of CCS, E2F1/E2F3 target genes were all showed significant (p<0.05), and these three gene sets still gave statistical significances after the survival analysis was applied on only early stage lung adenocarcinoma. The hazard ratios of CCS, E2F1 target genes and E2F3 target genes were 5.69, 3.32, and 3.96, respectively; all p-values were smaller than 0.002. We demonstrated that the three gene sets, which accountable for the activity of cell cycle, can be applied as prognostic factors for lung adenocarcinoma, including early stage patients. Our data inferred that tumor with higher activity of proliferation is malignant eventhough its size may still be small. This finding is valuable in predicting the survival of early stage lung adenocarcinoma patients and might be useful for making treatment decisions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1993.