A clinical metabolomics‑based biomarker signature as an approach for early diagnosis of gastric cardia adenocarcinoma

Abstract

Gastric cardia adenocarcinoma (GCA) has a high mortality rate worldwide; however, current early diagnostic methods lack efficacy. Therefore, the aim of the present study was to identify potential biomarkers for the early diagnosis of GCA. Global metabolic profiles were obtained from plasma samples collected from 21 patients with GCA and 48 healthy controls using ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry. The orthogonal partial least squares discrimination analysis model was applied to distinguish patients with GCA from healthy controls and to identify potential biomarkers. Metabolic pathway analysis was performed using MetaboAnalyst (version 4.0) and revealed that ‘glycerophospholipid metabolism’, ‘linoleic acid metabolism’, ‘fatty acid biosynthesis’ and ‘primary bile acid biosynthesis’ were significantly associated with GCA. In addition, an early diagnostic model for GCA was established based on the relative levels of four key biomarkers, including phosphorylcholine, glycocholic acid, L-acetylcarnitine and arachidonic acid. The area under the receiver operating characteristic curve revealed that the diagnostic model had a sensitivity and specificity of 0.977 and 0.952, respectively. The present study demonstrated that metabolomics may aid the identification of the mechanisms underlying the pathogenesis of GCA. In addition, the proposed diagnostic method may serve as a promising approach for the early diagnosis of GCA.

Novel metabolic biomarker for early detection and diagnosis to the patients with gastric cardia adenocarcinoma

“…30 Furthermore, we identified common downregulated metabolites in GCA patients, including glycoursodeoxycholic acid and LysoPC(14:0). 31 Glycoursodeoxycholic acid, a type of bile acid, plays a complex role in carcinogenesis. Traditionally, bile acids have been associated with the development of esophageal cancer, representing one facet of their impact.…”

Efficient plasma metabolic fingerprinting as a novel tool for diagnosis and prognosis of gastric cancer: a large-scale, multicentre study

“…In parallel, metabolic biomarkers, as the downstream products, are expected to provide real-time phenotype information of biosystems and developed as highly efficient targets for therapeutic intervention 46 47. Metabolic biomarkers have shown promising proof-of-concept results for GC diagnosis in previous study but remain largely inconclusive, due to traditional analytical tools and preliminary study design 12–20…”

“…Study design plays a fundamental role in the development of high-performance biomarker panel and thus provides precise insights into disease phenotype, regarding sufficient cohort size, advanced data interpretation method and multiple phases of biomarker development 51. For cohort size, previous works for metabolic analysis of GC were mainly carried out with small-scale single-centre cohorts (n=69–600) 12–16. In contrast, a total of 2208 subjects (including n=1944 in retrospective cohort and n=264 in prospective cohort) were enrolled in this study with well-defined inclusion and exclusion criteria, and their PMFs were recorded by NPELDI-MS, which incorporated advantageous of high throughout, desirable reproducibility and limited centre-specific effects that were designed for detection of large-scale multicentre cohort.…”

“…Further, compared with the upstream molecular biomarkers such as nucleic acids and proteins, small metabolites (molecular weight (MW) <1000 Da) as downstream molecular biomarkers directly reveal the phenotype of cancer 10 11. Notably, the available metabolites as GC biomarkers are still very limited, on small preliminary cohorts (69–600) 12–23. Therefore, panels of metabolic biomarkers are in demand, which should be constructed on a designer GC cohort, with multifunctions in both diagnosis and prognosis.…”

UPLC-Q-TOF/MS-Based Serum and Urine Metabonomics Study on the Ameliorative Effects of Palmatine on Helicobacter pylori–Induced Chronic Atrophic Gastritis

“…Glycerophospholipid metabolism was continually disturbed during CAG which has been demonstrated to be closely associated with the immune response. Glycerophospholipid levels are significantly reduced in GCA patients, indicated the disease related dysfunction in glycerophospholipid metabolism (Sun et al, 2020). As one of the subcategories of carbohydrate metabolism, Pentose and glucuronate interconversions is the basis for providing more carbohydrates to the gastrointestinal tract to resist the more complex environment caused by H. pylori.…”