Serum metabolomic signatures associated with gastric signet-ring cell carcinoma: A dual-platform mass spectrometry...

Gastric signet-ring cell carcinoma (GSRCC), a distinct subtype of gastric adenocarcinoma, is associated with increasing incidence and poor prognosis. The metabolic landscape remains poorly understood and non-invasive biomarkers for early detection are limited. The present study aimed to explore the metabolic signatures for GSRCC using metabolomics profiling. Serum samples from 8 treatment-naive patients with GSRCC and 10 healthy controls were analyzed using liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. Differential metabolites were identified through multivariate statistical analysis (principal component analysis, partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis) with a criteria of variable importance in projection >1, q<0.05 (Benjamini-Hochberg false discovery rate correction) and log₂ fold change >0.58. Metabolic pathway enrichment was performed using the Kyoto Encyclopedia of Genes and Genomes database. Key metabolites associated with routine clinical biochemistry parameters were analyzed in an independent cohort (35 patients with GSRCC and 35 controls). A total of 68 differential metabolites were identified (25 upregulated and 43 downregulated), predominantly comprising of phospholipids and amino acids. Pathway enrichment revealed significant alterations in 'choline metabolism in cancer', 'glycerophospholipid metabolism', 'pentose and glucuronate interconversions' and 'arginine biosynthesis' (all P<0.05; q<0.05). Among the enriched pathway-associated metabolites, phosphatidylcholine [PC(20:5(5Z,8Z,11Z,14Z,17Z)/20:2(11Z,14Z)] and dihydroxyacetone phosphate (DHAP) acyl ester showed the most significant differences (q<0.05) and demonstrated area under the curve values exceeding 0.80 (0.89 and 0.99, respectively). Patients with GSRCC exhibited significantly lower levels of cholinesterase, total protein, albumin and hemoglobin compared with controls (all P<0.01). Overall, the present study identified serum metabolomic alterations in GSRCC, highlighting the key role of choline and glycerophospholipid metabolism, with PC[20:5(5Z,8Z,11Z,14Z,17Z)/20:2(11Z,14Z)] and DHAP acyl ester representing exploratory candidate metabolic signatures associated with GSRCC, providing a foundation for future biomarker discovery.