Prognostic markers: Development of a tumour atlas in colorectal cancer

This project aims to generate clinically relevant RNA signatures from microdissected tumours for outcome and treatment evaluation in colorectal cancer.The development of molecular analytical techniques and their application to clinical diagnostic studies has been rapid. However, the reliable interpretation of results obtained from gene expression analyses is largely influenced by the selection of appropriate study material. Colorectal cancer biopsies contain multiple cell types, are multiclonal and are characterised by distinctive histopathologies with discrete gene expression profiles. As a result, gene expression profiles from bulk biopsies obscure clinically relevant expression signatures from areas associated with poor treatment outcome, such as those characterised by vascular and lymphatic invasion and lymphocytic infiltration. A critical consequence of this heterogeneity is that such samples are unable to provide robust expression signatures capable of accurate prognostic stratification of individual colorectal cancer patients following surgery. Our solution is to use microdissection to establish gene expression profiles from specific histopathological areas that are clinically relevant and associated with poor outcome. This will allow the development of a tumour atlas associating defined histopathological areas with specific gene expression profiles and treatment outcome. The picture shows a colorectal cancer that has successfully invaded a capillary blood vessel,

Our approach represents a systematic and novel approach to identifying RNA signatures that are more appropriate for predicting disease outcome than those obtained from bulk biopsies and should help define distinct gene expression features associated with high metastatic potential and poor treatment outcome in primary colorectal cancers.