Localization analysis of lysophosphatidylinositol in colorectal cancer using imaging mass spectrometry

The role of lipid metabolism, particularly lysophospholipids (LPLs), in cancer biology has recently attracted increasing attention. We previously demonstrated that lysophosphatidylinositol (LPI) concentrations were significantly higher in colorectal cancer (CRC) tissues than in normal tissues. In the present study, we used imaging mass spectrometry (IMS) to further analyze the spatial distribution of LPI and its precursor phosphatidylinositol (PI) in CRC tissues. We also examined the expression patterns of related metabolic enzymes and receptors using immunohistochemical staining (IHC) and in situ RNA hybridization. Regions-of-interest (ROI)-based quantitative analysis showed higher signal intensities of several LPI species, particularly 18:0 and 18:1 LPI, in cancer tissues than in adjacent normal tissues. The increased LPI species showed spatial distributions similar to those of PI species with similar fatty acid compositions. IHC demonstrated high expression of phospholipase DDHD domain containing 1 (DDHD1) and G protein-coupled receptor 55 (GPR55) in cancer tissues. In situ RNA hybridization revealed that GPR55 mRNA was barely detectable in normal tissues and weakly expressed in cancer tissues. This pilot study provides preliminary evidence that altered LPI metabolism and its associated signaling pathways may be involved in CRC biology. These findings warrant further investigation.