Mass Spectrometry Imaging for Tumour Subtype Classification.

The focus of this study will be the molecular characterisation of colorectal tumour cells and tissue samples by matrix-assisted laser desorption ionisation (MALDI) mass spectrometry (MS). MALDI-MS can generate characteristic molecular signatures from tissue samples that can be used to identify different phenotypes. In an imaging configuration the technique can also map tumour heterogeneity. The study brings together the Mass Spectrometry Imaging Group at WMIC, the Hypoxia and Therapeutics Group in the Manchester Pharmacy School, and the Colorectal and Peritoneal Oncology Centre at the Christie NHSFT, allowing access to biopsy and resected tumour samples that will be tested for DNA and RNA-based biomarkers (extended KRAS, NRAS, BRAF, MSI and PIC3CA) at the Manchester Centre for Genomics, for which charitable funding is secured). These biomarkers have been shown to predict response to chemotherapy and are of prognostic importance. Our commercial partner is Kratos Analytical (Trafford Park, Manchester) who will give access to their latest MALDI-MS instrument, the 7090 tandem imaging mass spectrometer as well as the iMLayer precision MALDI matrix deposition device for sample preparation. MALDI mass spectrometry data will be analysed using multivariate statistical approaches to differentiate phenotypes within and between tumours, correlating the corresponding mass spectral signatures with the DNA and RNA-based biomarkers mentioned above.
We will test the hypothesis that MS-derived molecular signatures from tumour samples correlate with known biomarker sub-types and that MS-based molecular profiling will help sub-divide this further. We will also explore concordance between the primary tumour and peritoneal metastases with regards to biomarkers and MS-deriver molecular signatures. This knowledge of tumour phenotypes is critical to the selection of 2nd line chemotherapy options. The imaging capability of the MALDI instrumentation will allow intra-tumour heterogeneity to be described and spatial correlations sought between a variety of mass spectrometry-derived molecular markers and IHC images.
Outcomes will include a better understanding of colorectal tumour sub-type and heterogeneity and a more rapid approach to tumour phenotyping.