Exploratory Insights into Gastric Cancer Metabolism Through Amino Acid and Acylcarnitine Profiling in Plasma Samples

<b>Background</b>: Gastric cancer ranks fifth among the most prevalent malignancies, with poor prognosis due to limited early-stage diagnosis. Metabolic reprogramming plays a central role in GC development, sustaining carcinogenic processes. <b>Methods</b>: In this study, flow-injection tandem mass spectrometry was used to analyse plasma amino acids and acylcarnitines in 62 gastric cancer patients and 70 healthy individuals. Metabolic profiles were correlated with clinical parameters, tumour histology, and recurrence. <b>Results</b>: Gastric cancer patients showed significantly reduced levels of Trp, Arg, Tyr, Met, and sum of aromatic AAs-metabolites usually implicated in supporting tumour cell growth and proliferation. At the same time, elevated unsaturated, hydroxylated, and dicarboxylic acylcarnitines suggest mitochondrial and peroxisomal dysfunction. Marked metabolic heterogeneity was observed across histological subtypes, with the indeterminate subtype exhibiting the most pronounced disruption in fatty acid oxidation and widespread acylcarnitine alterations. Decreased levels of C6DC-carnitine and Cit synthesis were correlated with higher tumour recurrence, warranting further confirmatory investigations. <b>Conclusions</b>: These findings underscore the value of plasma profiling of amino acids and acylcarnitines for understanding gastric cancer biology, revealing distinct metabolic adaptations reflecting tumour biology, histological subtype, and treatment response.