044 and 0.460 respectively, paired t-test, Figure 4). Interestingly,

TGFB1 BGJ398 ic50 expression showed step-wise increase from polyp, to normal, to tumour (P=0.016, ANOVA). Further analysis (Post-Hoc Tukey test) pointed out significant differences in expression between tumours and polyps (P=0.029), but not between tumours and TAN (P=0.345) and between polyps and TAN (P=0.914) (Figure 4). Figure 4 TGFB1 and its receptors expression in CRC tumour & normal tsssue The relationship between TGFB1, TGFBR1 and TGFBR2 was further investigated using Pearson correlation. Inhibitors,research,lifescience,medical No violation of the assumption of normality, linearity and homogenecity was ensured before conducting further analysis. There was positive correlation between all the variables in both tumour and TAN colorectal tissues with high expression level of the ligand Inhibitors,research,lifescience,medical associated with high expression of the receptors (Table 3). The relation of TGFB1 and its receptors expression levels and the clinico-pathological parameters were examined using ANOVA and t-test (Figure 4). Although high level of TGFB1 was documented in tumours compared to normal colorectal tissues, we noticed an association of TGFB1 down-regulation and lymphovascular invasion (P=0.035). Both TGFBR1 and TGFBR2 were under-expressed in proximal colon, however, the difference was only significant for TGFBR2 (P=0.003). TGFBR1 showed reduced expression Inhibitors,research,lifescience,medical in association with advanced disease clinicopathological

parameters like tumour size, poor differentiation, advanced nodal stage, advanced Dukes’ stage and tumour invasion and metastasis

Inhibitors,research,lifescience,medical (Table 3), However, these associations were only significant in relation to bowel wall involvement (P<0.001), and raised CEA serum level (P=0.045). Down-regulation of TGFBR2 was significantly associated with increased bowel wall involvement (P=0.006), in colon cancer compared to rectal cancer (P=0.031) and in association with perineural (P=0.030) and lymphovascular Inhibitors,research,lifescience,medical invasion (P=0.012). No significant differences were identified in CEACAM5 expression levels in tumour compared to TAN colorectal tissues (P=0.981, t-test). In addition, no enough significant correlations were found between CEACAM5 expression and the CEA serum level (r=-134, n=79, P=0.240). Higher expression of CEACAM 5 was associated with moderately differentiated tumours (P=0.016) and local (P=0.002) and lymphovascular invasion (P=0.019) (Kruskal-Wallis and Mann-Whitney tests, Table 3). Neoadjuvant therapy and colorectal cancer genes expression In the cohort of rectal cancer patients (n=58) we analysed the differences in gene expression in patients who had neoadjuvant chemoradiation (n=25) compared to those who did not (n=33) using t-test. Univariate analysis of variance was further conducted to test for interaction effect and to control for confounding factors. We demonstrated decrease expression of CDH17 (P=0.020) and CEACAM5 (P=0.032) and increase expression of CXCL12 (P<0.001), CXCR4 (P=0.004) and MUC2 (P=0.