Metabolic Reprogramming of Gastric Cancer Revealed by a Liquid Chromatography-Mass Spectrometry-Based Metabolomics...

Area of Science:

• Metabolomics and Cancer Biology
• Biochemical pathways in tumorigenesis
• Biomarker discovery for gastric cancer

Background:

• Gastric cancer (GC) is a major global health concern with poorly understood pathological mechanisms.
• Metabolic reprogramming is a hallmark of cancer, and understanding these changes in GC is vital for effective treatment and prevention.
• Identifying specific metabolic alterations can lead to novel diagnostic and therapeutic strategies for GC.

Purpose of the Study:

• To identify significant metabolite and pathway alterations associated with gastric cancer development.
• To explore metabolic subnetworks related to tumorigenesis and different TNM stages of GC.
• To discover potential biomarkers for GC diagnosis and prognosis.

Main Methods:

• Non-targeted metabolomics using liquid chromatography-mass spectrometry on paired GC and adjacent normal tissues from 80 patients.
• Statistical analyses (univariate and multivariate) to compare metabolic profiles between tumor and normal tissues.
• Differential correlation network analysis and a novel network analysis method (NAM) to identify significant metabolic pathways and subnetworks.

Main Results:

• Over 50% of annotated metabolites showed significant alterations in GC tissues.
• Phosphatidylcholine (PC)_30_0 and fatty acid C20_3 exhibited high diagnostic performance (AUCs > 0.91).
• Fatty acid metabolism reprogramming was evident, with elevated medium-chain acylcarnitines and increased medium-chain acyl-CoA dehydrogenase activity. Two TNM-stage-specific subnetworks centered on choline and carnitine C4_0-OH were identified.

Conclusions:

• Significant alterations in fatty acid metabolism and TNM-stage-specific metabolic subnetworks were identified in GC tissues.
• These findings provide a deeper understanding of metabolic reprogramming in gastric cancer.
• The identified metabolic signatures may serve as targets for future research in GC prevention and treatment.