3572 Background: Despite substantial progress in molecular pathogenesis of colon cancer (CC), no reliable biomarkers of outcome have yet been identified in patients with resected stage II-III CC. Methods: We analyzed genome-wide mRNA expression profiles in 20 stage II or III left side CC from 10 patient who developed metastasis (M+) and 10 disease free patients followed up for at least 4 years (M-) using high-density oligonucleotide microarrays (Agilent technology). RNA from tumor tissue (T) was hybridized against normal tissue (NT) from the same patient and each experiment was replicated 4 times (with 2 dye-swaps). The goal was to select genes both differentially expressed between T and NT and between M+ and M-. A tissu-array was constructed using 212 stage II and III resected CRC (164 CC, 64 rectal cancers) and their matched NT. For survival analysis, immunohistochemistry (IHC) data was dichotomized at the median value. Results: Analysis of microarray data yielded 27 genes that had a 2-fold difference between the expression in T and NT in at least 5 out of 20 patients and for which the average expression was significantly different between M+ and M- (p<0.01, t-test). Among the 6 most differentially expressed genes between M+ and M- in T, 4 of them were found to be involved in interferon γ pathway and could be evaluated by IHC: CXCL9, CXCL13, PPARγ, THSD. In order to assess macrophage and natural killer (NK) cell infiltration, CD68 and CD57 were also analyzed. Intensity was measured by semi-quantitative scores for the first 4 genes and by the number of infiltrating cells for the others. CXCL9, PPARGγ, CXCL13, CD57 and CD68 were significantly underexpressed in T as compared to NT (p<0.0001, paired t-test). The logrank test stratified by cancer site indicated that high IHC expression of CD57 possessed a significantly better recurrence-free survival (RFS) than those low expression (p=0.004). Multivariate Cox analysis identified tumor site (p=0.001), node stage (p<0.001) and CD57 (p=0.002) as independent predictors of RFS. Conclusions: NK cell infiltration within colorectal cancers is associated with prolonged recurrence-free survival in stage II and III CRC. No significant financial relationships to disclose.
Genome-wide association analysis identifies SNPs predictive of in vitro leukemic cell sensitivity to cytarabine in pediatric AML