MRC DTP in Precision Medicine

Spatially resolving the squamous signature of metastatic colorectal cancer and deconvoluting the immune microenvironment

Supervisors

Colin Steele, School of Cancer Sciences, University of Glasgow 

Kevin Myant, School of Informatics and Institute of Genetics and Cancer, University of Edinburgh

Ava Khamseh, School of Informatics and Institute of Genetics and Cancer, University of Edinburgh

 

Summary

Colorectal cancer is a common disease and despite surgery for primary disease recurrence rates are high. Better understanding of molecular subtypes of the disease will permit personalized stratification of therapies in future. Spatial biological approaches are revolutionizing the understanding of disease, permitting assessments of tumour, stromal and immune cell interactions within tumours. Greater understanding of patient disease, and factors that determine recurrence at different sites will permit enhanced surveillance, and an opportunity to identify and intervene early in these patients. The Myant and Steele labs have determined an RNA signature that delineates patients with particularly poor outcomes that metastasise readily and transcription factors that influence regulation of a squamous/basal (invasive) cell state.

The Steele, Edwards and Jamieson labs have collaborated on spatial transcriptomic assessment of colorectal cancer and have datasets to single cell level in both primary and secondary disease. We will integrate the squamous/basal cell phenotype in our large patient cohort, determine which patients express this phenotype, and how this influences coordination of the microenvironment through immune cell deconvolution and cellular neighbourhood analysis. We will identify features that may be modulated in this setting and take these into in vivo studies in accurate models of metastasis.