A COMPARISON BETWEEN HIGH MORTALITY RISK GENES IN LUNG ADENOCARCINOMA AND PROGRESSION FREE INTERVAL (PFI) GENES IN LUAD AND LUSC: A LARGE TCGA POPULATION ANALYSIS.

OBJECTIVE In 2015 a molecular expression signature [cell cycle progression (CCP) score] has been validate by Bueno et al. to identify patients with a higher risk of cancer-related death after surgical resection of early stage (I-II) lung adenocarcinoma. Aim of our study is to define if the same 31 genes have an impact on LUAD and LUSC progression free interval (PFI), not only in early but also in locally advanced stages. METHODS We retrospectively analyzed the association between the expression of 31 previously identified recurrence-related cell cycle genes and PFI. Data have been extracted from TGCA database including 741 patients from stage I to stage III affected by LUAD and LUSC. Results were reported as the hazard ratio (HR) related to a 1-unit increase in genes’ FPKM-UQ, based on sex- and age-adjusted robust Cox analysis stratified by clinical stage. Statistical significance was set at p < 0.05. RESULTS 741 patients were analyzed. For LUAD and LUSC patients in stage I, the genes most associated with PFI are DTL (HR=1.39, p=0.0005) and CDK1 (HR=1.27, p=0.0475), respectively. For stage II patients, no gene was associated to PFI. For stage III patients, the most associated gene is PTTG1 (HR=2.08, p=0.000 and HR=2.14, p=0.0000, respectively) (Fig. 1). CONCLUSIONS In this study we show for the first time the most expressed genes which may have a huge impact on progression free interval (PFI) in LUAD and LUSC. This would highlight the most “sensible” genes which may need to be further investigated as “protective” against cancer.