Colorectal cancer represents a significant public health burden, with over 1 million new cases and more than 0.5 million deaths worldwide every year. Outcomes for patients with early-stage CRC are variable even within the same tumour stage. Five year survival rates range from 72% to 83% in stage II disease and from 44% to 83% in stage III disease. Tumour stage however, continues to play a fundamental role in the management of patients as the most powerful and reliable predictor of prognosis. It also serves as the operational basis of choosing the most appropriate therapy and for evaluating the efficacy of different therapeutic methods through comparison of expected survival rates.
There is a clear need for new factors, either morphologic or molecular that could more precisely stratify patients with the same tumour stage into different risk categories for planning the most appropriate treatments. This is particular true for earlier-stage disease.
There are at least 12 different laminin chains, combinations of which give rise to at least 16 different laminin isoforms. The inventors have identified that a more sophisticated analysis of laminin isoform expression can generate valuable information about tumour aggressiveness and sensitivity to targeted treatments. Survival outcomes were analysed in correlation with expression of multiple laminin chain subunit combinations. The UoM panel provides very good discrimination between the small proportion of tumours that progress and those that do not. Results achieved to date also correlate expression of epithelial laminins and aggressiveness of cancer cells / sensitivity to targeted inhibitors.
Figure 1. Stage II patients. Stage II tumours represent the greyest area in CRC prognosis. A significant proportion of these tumours will progress towards metastasis although the primary tumour is removed. The UoM laminin gene panel provides very good discrimination, much better than that provided by single laminin chain quantification (eg. LAMC2) which has previously thought to be of prognostic interest.
Figure 2. Colorectal cancer cells that have a total laminin score (HT55, HT29 and SW480) also have lower sensitivity to Folfox in comparison to colorectal cancer cells that have a lower total laminin score (Colo205, Colo320HSR and RK0). Sensitivity was determined by exposing cells to increasing concentrations of FOLFOX and determining IC50.
Australian provisional patent application filed.
Associate Prof. Frederic Hollande
Dr Sergey Rodin
Dr Oscar Simonson
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