However, the differences only persisted for CXCL12 (P=0.035) and CXCR4 (P=0.001) after univariate analysis (HDAC inhibitor Figure 5). Figure 5 Dysregulation of gene expression in response to neoadjuvant CRT. Neoadjuvant chemoratiation associated with sigificat up-regulation of CXCL12 (A, univariate analysis, P=0.0035) and CXCR4 (B, univariate analysis, P=0.001) expression Interestingly, Inhibitors,research,lifescience,medical expression levels of CDH17 (P=0.003), CEACAM5 (P=0.036), CXCL12 (P≤0.001) and CXCR4 (P=0.003) significantly correlated with Mandard tumour regression grade (TRG).

Higher expression of CXCL12 and CXCR4 was noticed in good responders (TRG1, TRG2 and TRG3) compared to poor responders (TRG4 and TRG5) in contrast to the expression levels of CDH17 and CEACAM5 which were lower in Inhibitors,research,lifescience,medical good responders (ANOVA test, Figure 6) Figure 6 Correlation of gene expression with tumour regression grade. Increased expression of CXCL12 (A, P<0.001) and CXCR4 (B, P=0.003) was associated with lower TRG (good response) in constrast to CDH17 (C, P=0.003) and CEACAM5 (D, P=0.036) Discussion Colorectal cancer is the fourth most common cancer in men and the third most common cancer in women Inhibitors,research,lifescience,medical worldwide (34).

In the USA, colorectal cancer is the second most common cause of cancer death among men aged 40 to 79 years and accounts for 9% of all cancer related deaths (35). In Ireland, the National Cancer Registry predicts that the incidence of colorectal cancer will increase from 2,111 cases in 2005 to 5,537 in 2035 (36), indicating a more than 100% increase over the next 30 years. In this setting of increasing disease burden, translational Inhibitors,research,lifescience,medical research is of vital importance to clinical advancement. At the molecular level, activation of oncogenes and

inactivation of tumour suppressor genes Inhibitors,research,lifescience,medical (3) are processes known to be involved in colorectal carcinogenesis. Additionally, abrogation of mismatch repair systems (37) contributes to some colorectal cancers. Nevertheless, exactly how these genetic alterations bring about the development and progression of colorectal carcinomas remains to be resolved. To complicate the picture, accumulation of mutant genes in neoplasms tends to be accompanied by other genetic and epigenetic changes over including loss of heterozygosity, inactivation of important genes by methylation or loss of imprinting (4) or gene amplifications, all of which can alter gene expression profiles. Therefore, genome wide monitoring of gene expression is of great importance if we are to disclose the numerous and diverse events associated with carcinogenesis. Molecular profiling, a tool of genome monitoring, is an attempt to identify the different combinations of genetic events or alternative pathways that may be represented by cancers of a similar type.