Deciphering the circulating lipidome signature associated with physical performance in gastric cancer patients: an exploratory study

INTRODUCTION: Physical performance strongly influences peri-treatment outcomes in gastric cancer (GC), yet simple molecular markers reflecting functional status are lacking. Lipidomics may help identify circulating biomarkers linked to physical fitness. OBJECTIVES: To assess whether physical performance is associated with distinct plasma lipidomic profiles in GC patients. METHODS: Nineteen male GC patients (60-75 years) from the PROTECT trial were classified as high- (HighP) or low-performance (LowP) based on the 6-min walk test. Plasma lipidomics (LC-MS/MS) quantified 232 lipid species and a total of 25 fatty acids were quantified by gas chromatography-MS. Multivariate and univariate analyses, group comparisons, and correlations examined associations with clinical, anthropometric, and fitness parameters. RESULTS: Lipid profiles differed by performance status. HighP patients showed higher phosphatidylinositol (PI 36:2) and trends toward increased plasmalogen phosphatidylethanolamines (PE), whereas sphingomyelin (SM 43:2) was higher in LowP patients. Plasmenyl-PE species correlated positively with functional tests, muscle mass, body mass index, and nutritional status; SM 43:2 correlated negatively. Acylcarnitines showed minimal associations. CONCLUSION: GC patients with different physical performance status display distinct circulating lipid signatures. PI 36:2, PE plasmalogens, and SM 43:2 species appear linked to physical fitness, suggesting potential value as preoperative biomarkers. Validation in larger cohorts is warranted.