Newnham et al. BMC Cancer 2011, 11:93 http://www.biomedcentral.com/1471-2407/11/93 Page 7 of 11 Figure 3 Survival curves based on recurrence differential gene list. A. Recurrence free survival curve for our dataset grouped by recurrence differential gene list. B: Kaplan Meier survival curve for external dataset GSE11117 using 40 transcripts matched to our recurrence differential gene list to classify. ‘non-metastatic’ tumours, neither of which have been previously implicated in malignancy. Similarly, correla- tion of transcriptional and genomic data identified only 3 genes with concordant differences in recurrence and survival comparisons - SMARCA2, MINK and RECK. Discussion The clinical, demographic and pathologic characteristics of this NSCLC cohort are consistent with the published literature. The transcriptional and genomic profiles identified in this study should therefore be generalisable to other patients with early-stage NSCLC. The tumour samples analysed demonstrated substantial genomic instability, with comparisons between subgroups failing to demonstrate any significant difference. Previous stu- dies of copy number changes in NSCLC have found no association between age, gender, histology, stage or tumour grade and the degree of genomic instability [19-21]. The absence of difference in the degree of genomic abnormalities between KRAS mutant and wt tumours is interesting, as both our transcriptional and genomic data imply enhanced activity of genes involved in chromosome structure and organisation in KRAS mutant tumours. We recognise that there were a small number of KRAS mutant tumours available for compari- son and this may have limited our analysis. Consistent with previously reported studies [9-16], the major differences in copy number and gene expression profiles between AC and SCC of the lung involved chro- mosome 3q. The strong independent correlation with amplification and over-expression at this locus suggests a causal relationship in SCC for genes in this region which warrant further investigation. These include TP73L, a gene extensively implicated in SCC, whose expression was most strongly correlated with the SCC phenotype, and which has been previously reported to be a putative oncogene [22-32]. While the role of TP73L in squamous cell pathogenesis remains unclear, a recent study of SiRNA mediated TP73L inhibition in SCC resulted in reduced cell survival with maintenance of squamous characteristics [28]. These results suggest that TP73L is important in SCC cell survival. Other genes previously shown to be over-expressed in SCC were included in our differentiating list (CSTA [33,34], FGFBP1), and warrant functional validation. The differential copy number and expression levels between AC and SCC of TNFSF10/TRAIL and ABCC5, which have roles in apoptosis and chemoresistance respec- tively, may have implications for treatment of NSCLC. Recently published clinical data [35] suggest there are his- totype-specific differences in response to systemic thera- pies. Validation of the differential activity of the roles of these genes and sensitivity to conventional and novel che- motherapeutic agents may be an area for future research. Published data on the relationship between TP53 muta- tions and histotype in NSCLC is conflicting [36,37]. SCC were associated with more frequent TP53 mutations than AC in our dataset. Cigarette smoking is a causal factor for both SCC phenotype and TP53 mutation [37]. However, we also observed a correlation between 3q amplification and TP53 mutations in AC samples. This suggests that the apparent association between TP53 mutations and SCC may be mediated by the relationship between TP53 muta- tions and amplification of regions of 3q. We caution that this study is underpowered to draw strong conclusions regarding the role of TP53 in NSCLC pathogenesis. Tumours possessing mutations of KRAS express genes playing key roles in cell growth, chromosome organisation