1H NMR profiling in colorectal cancer

Abstract

Colorectal cancer remains a major cause of death and illness in Western society. Although advances have been made in its management over the past 2 decades, many challenges with appropriate treatment targeting, diagnosis and management remain. Addressing these challenges through the approach of ‘personalised healthcare’ is of increasing interest to researchers. This has been facilitated by recent advances in metabonomic techniques. This approach involves the investigation of metabolic consequences of disease downstream of the disease process, including the complex interaction between host and environment.

Using 1H NMR spectroscopy, colorectal cancer tissue was analysed on patients operated on between 2007 and 2009. The first study in this thesis identifies the metabolic phenotype associated with the disease, and attempts to relate this to what is known about colorectal and other cancer metabolism. The second study utilises multivariate regression analysis to develop discriminatory models and panels of metabolites to differentiate between cancer stages and other clinical and pathological features of the tissue. In the third study, this approach was applied to an in-vitro cell model of 5-FU chemotherapy resistance to determine the metabolic pathways associated with this resistance.

A distinct metabolic profile discriminating normal from cancerous tissue was identified. No such profile was able to discriminate tissue on the basis of cancer stage. Discreet metabolic changes were associated with 5-FU chemoresistance but were too few to make assumptions about mechanism.

Colorectal cancer joins other solid tumours in expressing a distinct metabolic phenotype and metabonomic techniques provide insight into the mechanisms underlying the disease.