Nevertheless, this is the first study to explore the relation of TGFB1 and its receptors mRNA in colorectal cancer using RT-PCR. Moreover, the large cohort of patients in this study gives it further advantage compared to the other studies. Other genes shown to be potential biomarkers in this study included CDH17, FABP1, IL8, MUC2 and PDCD4. In colorectal cancer, CDH17 expression was only investigated at protein level using IHC and immunoblotting. Hinoi et al. examined the

protein expression in human colorectal cancer cell lines. In their study, CDH17 was not detected Inhibitors,research,lifescience,medical in cell lines showing dedifferentiated phenotypes (43). This was further confirmed by Takamura et al. who examined the CDH17 expression Inhibitors,research,lifescience,medical in four cell lines and 45 human primary colorectal carcinoma using monoclonal antibodies. In cell lines the protein was expressed in differentiated but not the dedifferentiated phenotypes while in tissues reduced CDH17 expression was associated with high Rapamycin FDA tumour grade, advanced stage and lymphatic invasion and metastasis (44). Moreover, Kwak et al. found reduced expression in 51% of the 207 colorectal cancers he studied using immunohistochemistry and he

significantly correlated down-expression of CDH17 with poor survival and lymph nodes metastasis (45). To our knowledge, this is the first study to investigate CDH17 mRNA in colorectal cancer using RQ-PCR. Our findings Inhibitors,research,lifescience,medical support the above reports and confirm that down-regulation of CDH17 in colorectal cancer is associated with poor differentiation, raised CA19.9 tumour marker serum level and local tumour invasion indicated by increase bowel wall involvement. Interestingly, CDH17 expression correlated with increased tumour diameter and tumour thickness (indices of intraluminal Inhibitors,research,lifescience,medical tumour growth)

and decreased with increased bowel wall involvement (index Inhibitors,research,lifescience,medical of local tumour invasion). Those findings could be explained by the adhesion function of the protein. Generally, for the tumour to grow in diameter and thickness it needs to retain adhesion molecules expression, while loss or inactivation of those adhesion molecules correlate with inhibition of cell aggregation and promotion of tumour invasiveness. This finding may highlight the potential role of CDH17 as a marker for rectal cancer surgical management planning. In other wards, decrease level of CDH17 may indicate GSK-3 local invasion of tumour and therefore total BMS-907351 mesorectal excision (TME) will be indicated. Evidence of dysregulated FABP1 gene expression has been reported in colorectal gene expression array datasets (5,46), however, little is known of its expression profile with regard to clinical data. Lawrie et al. identified consistent loss of FABP1 in tumour compared to normal colon and also noted the association of decreased protein expression and poorly differentiated tumours and large adenomas (47).