Phospholipid MALDI Imaging Mass Spectrometry Stratification of Colorectal Cancer Liver Metastasis Clinical Biopsies

摘要

Colorectal cancer is the third leading cause of cancer mortality worldwide. Death from colorectal cancer is due to metastatic disease and the liver is the most common site of metastasis. Many treatment options are available including surgery and chemotherapy but reliable prognostics for treatment and assessment of treatment response are limited and thus new technologies are sought as a solution. Within our work, MALDI Imaging Mass Spectrometry (MALDI-IMS) of phospholipids using 1,5-diaminonapthalene (DAN) matrix is proposed as a solution to bridge this clinical gap. The potential clinical utility of phospholipid IMS has been demonstrated in a number of applications, however, IMS tissue studies of large cohorts needed for clinical validity require robust and validated approaches for data interpretation due to the multivariate nature and size of IMS datasets. Within our work we propose a workflow for mining of histologies for characteristic lipids and generate robust signatures for classification of tissue topography on previously unknown CRCLM samples. When taken together, these results demonstrate the potential of our workflow as a clinical aid and simultaneously as a tool for generating biological hypotheses directly from clinical origin.