BACKGROUND: Although screening programmes of smokers have detected resectable early @entity2 more frequently than expected, their efficacy in reducing mortality remains debatable. To elucidate the biological features of computed tomography (CT) screening detected @entity2 , we examined the mRNA signatures on @entity5 according to the year of detection, stage and survival. METHODS: Gene expression profiles were analysed on 28 @entity1 (INT-IEO training cohort) and 24 @entity1 of Multicentre Italian Lung Detection (MILD validation cohort). The gene signatures generated from the training set were validated on the MILD set and a public deposited DNA microarray data set (GSE11969). Expression of selected genes and proteins was validated by real-time RT-PCR and immunohistochemistry. Enriched core pathway and pathway networks were explored by GeneSpring GX10. FINDINGS: A 239-gene signature was identified according to the year of @entity5 detection in the training INT-IEO set and correlated with the @entity1 ' outcomes. These signatures divided the MILD @entity1 into two distinct survival groups independently of @entity5 stage, size, histopathological type and screening year. The signatures can also predict survival in the clinically detected @entity5 (GSE11969). Pathway analyses revealed @entity5 detected in later years enrichment of the @entity10412 / @entity983 / @entity584 pathway, with up-regulation of @entity60796 , @entity2393 and down-regulation of @entity4012 . Analysis of normal lung tissue from INT-IEO cohort produced signatures distinguishing @entity1 with early from late detected @entity5 . INTERPRETATION: The distinct pattern of "indolent" and " @entity146 " @entity5 exists in @entity2 according to the gene expression profiles. The early development of an @entity146 phenotype may account for the lack of mortality reduction by screening observed in some cohorts.

Gene Signatures Stratify Computed Tomography Screening Detected XXXX in High-Risk Populations.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity146 :: ('MESH:D001523', 'Disease') :: ['aggressive'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancers', 'tumours', 'tumour'] @entity2 :: ('MESH:D008175', 'Disease') :: ['CT-screening detected lung cancer', 'lung cancers', 'lung cancer'] @entity584 :: ('207', 'Gene') :: ['AKT'] @entity60796 :: ('5170', 'Gene') :: ['PDPK1'] @entity10412 :: ('5293', 'Gene') :: ['PI3K'] @entity983 :: ('5728', 'Gene') :: ['PTEN'] @entity4012 :: ('2308', 'Gene') :: ['FOXO1A'] @entity2393 :: ('3688', 'Gene') :: ['ITGB1']
@entity2 :: (MESH:D008175,Disease) :: ['Lung Cancer']
