Spatially-resolved characterization of the metabolic and N-glycan alterations in colorectal cancer using matrix-assisted laser desorption/ionization mass spectrometry imaging†

Abstract

Colorectal cancer is the second leading cause of cancer-related deaths worldwide, and its development typically involves complex metabolic reprogramming. By mapping the spatial distributions of metabolites and N-glycans in heterogeneous colorectal cancer tissues, we can elucidate cancer-associated metabolic and N-glycan changes. Herein, we combine mass spectrometry imaging-based metabolomics and N-glycomics to characterize the spatially resolved reprogramming of metabolites and N-glycans in colorectal cancer tissues. The metabolic characteristics of different regions of colorectal cancer were evaluated through the utilization of orthogonal partial least squares discriminant analysis. In combination with metabolic pathway enrichment analysis, significant alterations were identified in the fatty acid metabolism, arginine and proline metabolism of colorectal cancer. Cancer cell regions exhibited a marked upregulation of saturated fatty acids, monounsaturated fatty acids, polyamines, and histidine. Additionally, we discovered that the high-mannose N-glycans were predominantly distributed in tumor tissue regions, whereas complex N-glycans were more commonly found in the normal tissue regions adjacent to the tumor. Such findings provide new insights into the spatial signatures of metabolites and N-glycans in colorectal cancer, thereby offering a crucial basis for the diagnosis of colorectal cancer and potential vulnerabilities that might be targeted for cancer therapy.