Key Lipid Reprogramming Revealed in Gastric Signet Ring Cell Carcinoma by Spatial Mass Spectrometry Metabolomics

Gastric signet ring
cell carcinoma (GSRC) is an aggressive subtype
of gastric cancer (GC) with a poor prognosis. The lack of a systematic
molecular and metabolic heterogeneity overview has led to slow progress
in clinical practice. This study used mass spectrometry imaging (MSI)
to investigate the metabolic landscape of GSRC in GC tissue with various
differentiation grades. Our comprehensive spatial profiling of metabolites
and lipids unveiled distinct metabolic signatures across different
tissue subregions. A substantial number of lipidomic biomarkers associated
with GSRC were identified, including phosphatidylethanolamine N-methyl (PE-NMe), phosphatidylethanolamine (PE), sphingomyelin
(SM), diacylglycerol (DG), phosphatidic acid (PA), and phosphatidylcholine
(PC), which may provide insights into its pathogenesis and potential
therapeutic targets. Furthermore, multi-omics network analysis revealed
intricate metabolic pathways involved in GSRC progression. Our findings
highlight the importance of understanding the metabolic heterogeneity
of GSRC and pave the way for future studies exploring its clinical
implications and therapeutic strategies.