Plasma sample based analysis of gastric cancer progression using targeted metabolomics

Abstract

Gastric carcinogenesis is a multifactorial process described as a stepwise progression from non-active gastritis (NAG), chronic active gastritis (CAG), precursor lesions of gastric cancer (PLGC) and gastric adenocarcinoma. Gastric cancer (GC) 5-year survival rate is highly dependent upon stage of disease at diagnosis, which is based on endoscopy, biopsy and pathological examinations. Non-invasive GC biomarkers would facilitate its diagnosis at early stages leading to improved GC prognosis. We analyzed plasma samples collected from 80 patients diagnosed with NAG without H. pylori infection (NAG−), CAG with H. pylori infection (CAG+), PLGC and GC. A panel of 208 metabolites including acylcarnitines, amino acids and biogenic amines, sphingolipids, glycerophospholipids, hexoses, and tryptophan and phenylalanine metabolites were quantified using two complementary quantitative approaches: Biocrates AbsoluteIDQ®p180 kit and a LC-MS method designed for the analysis of 29 tryptophan pathway and phenylalanine metabolites. Significantly altered metabolic profiles were found in GC patients that allowing discrimination from NAG−, CAG+ and PLGC patients. Pathway analysis showed significantly altered tryptophan and nitrogen metabolic pathways (FDR P < 0.01). Three metabolites (histidine, tryprophan and phenylacetylglutamine) discriminated between non-GC and GC groups. These metabolic signatures open new possibilities to improve surveillance of PLGC patients using a minimally invasive blood analysis.

Live single cell mass spectrometry reveals cancer‐specific metabolic profiles of circulating tumor cells

“…Furthermore, eicosanoids were also observed to be more abundant in CRC CTCs, which is further corroborated by other studies done on this cancer type . Glycerophospholipids were noticed to be elevated in GC CTCs, which also concurs with recent reports …”

Characterization of bulk phosphatidylcholine compositions in human plasma using side-chain resolving lipidomics

“…AbsoluteIDQ TM p150 and p180 kits have emerged as established measurement kits for quantification of phospholipids, such as PCs, in blood from thousands of participants in large epidemiological cohorts (11,12,15,16,20,(35)(36)(37)(38)(39) and in projects using a variety of human and non-human sample matrices (40)(41)(42)(43)(44). As the kits quantify PCs on the level of lipid species, each PC measure is composed of isobaric PCs (within mass resolution) with different combinations of fatty acid chain lengths and degrees of desaturation for the two residues.…”

“…Today, the availability of modern high throughput lipidomics approaches allows quantification of numerous PCs in thousands of blood samples from epidemiological cohorts. In various large-scale genome-wide and metabolome-wide association studies, many of these PCs have been reported to associate with common genetic variants and various diseases such as Alzheimer's disease (9,10), type 2 diabetes (11)(12)(13), metabolic syndrome (14), coronary artery disease (15), and gastric cancer (16).…”

Undetectable free aromatic amino acids in nails of breast carcinoma: Biomarkers discovery by a novel metabolite purification VTGE system

“…Intra-and inter-tumor heterogeneity at both cellular and non-cellular levels are depicted as the basis of origin, progression and drug response in breast cancer (7)(8)(9)(10). The elucidation of metabolic heterogeneity at tumor microenvironment and macroenvironment level is important in the perspective of biomarkers development and future interventions in breast cancer (11)(12)(13)(14)(15)(16).…”